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TDMS Study 97013-97 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 11/04/03       
EXPERIMENT: 97013 TEST: 97                                                                                     TIME: 12:03:40       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: 97013K       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
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                                                           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: 11/04/03       
EXPERIMENT: 97013 TEST: 97                                                                                     TIME: 12:03:40       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: 97013K       
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                                                                                    
-----                                 ----------                                                                                    
Kidney: Renal Tubule                   Degeneration                                                                                 
                                       Dilatation                                                                                   
Skin                                   Hyperplasia                                                                                  
Spleen                                 Hematopoietic Cell Proliferation                                                             
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Kidney                                 Casts Protein                                                                                
Liver                                  Inflammation                                                                                 
Liver: Hepatocyte                      Fatty Change                                                                                 
                                       Vacuolization Cytoplasmic                                                                    
Spleen                                 Hematopoietic Cell Proliferation                                                             
Thymus                                 Atrophy                                                                                      
===============================================================                                                                     
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMO
DICHLOR                                                                                                                             
                                         Terminal Sacrifice at 42 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)        |     7/10 (70%)   3/10 (30%)   6/10 (60%)   7/10 (70%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     7/8.57       3/6.13       6/7.52       7/8.24      |0/7.66       0/9.86       0/9.08       0/8.21       | 
|POLY-3 PERCENT (g) |     81.7%        48.9%        79.8%        85.0%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     5/6 (83%)    3/6 (50%)    6/6 (100%)   7/8 (88%)   |0/7 (0%)     0/9 (0%)     0/9 (0%)     0/7 (0%)     | 
|FIRST INCIDENCE    |     128          288 (T)      288 (T)      288 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.503N     P=0.108N     P=0.514N     P=0.357N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.411      P=0.223N     P=0.719N     P=0.687     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.419      P=0.229N     P=0.637N     P=0.671     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.420      P=0.201N     P=0.765      P=0.721     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.578      P=0.135N     P=0.426N     P=0.595N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.353      P=0.089N     P=0.500N     P=0.686N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.296      (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)        |     0/10 (0%)    1/10 (10%)   2/10 (20%)   0/10 (0%)   |5/10 (50%)   6/10 (60%)   4/10 (40%)   7/10 (70%)   | 
|POLY-3 RATE (b)    |     0/6.94       1/6.13       2/7.52       0/8.24      |5/9.04       6/9.86       4/9.08       7/9.20       | 
|POLY-3 PERCENT (g) |     0.0%         16.3%        26.6%        0.0%        |55.3%        60.8%        44.0%        76.1%        | 
|TERMINAL (d)       |     0/6 (0%)     1/6 (17%)    2/6 (33%)    0/8 (0%)    |3/7 (43%)    6/9 (67%)    4/9 (44%)    5/7 (71%)    | 
|FIRST INCIDENCE    |     ---          288 (T)      288 (T)      ---         |126          288 (T)      288 (T)      185          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.536N     P=0.500      P=0.229      (e)         |P=0.270      P=0.613N     P=0.353N     P=0.383      | 
|POLY 3             |     P=0.542N     P=0.475      P=0.239      (e)         |P=0.280      P=0.584      P=0.497N     P=0.332      | 
|POLY 1.5           |     P=0.572N     P=0.461      P=0.233      (e)         |P=0.293      P=0.572      P=0.493N     P=0.342      | 
|POLY 6             |     P=0.514N     P=0.490      P=0.243      (e)         |P=0.269      P=0.577      P=0.500N     P=0.318      | 
|LOGISTIC REGRESSION|     (e)          P=0.500      P=0.229      (e)         |P=0.303      P=0.517      P=0.478N     P=0.339      | 
|COCH-ARM / FISHERS |     P=0.620N     P=0.500      P=0.237      (e)         |P=0.296      P=0.500      P=0.500N     P=0.325      | 
|ORDER RESTRICTED   |     P=0.272N     (e)          (e)          (e)         |P=0.272      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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                                                                                                                           | 
|     Casts Protein                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/10 (30%)   1/10 (10%)   0/10 (0%)    1/10 (10%)  |1/10 (10%)   2/10 (20%)   6/10 (60%)   0/10 (0%)    | 
|POLY-3 RATE (b)    |     3/7.85       1/6.13       0/7.52       1/8.24      |1/7.66       2/9.86       6/10.00      0/8.21       | 
|POLY-3 PERCENT (g) |     38.2%        16.3%        0.0%         12.1%       |13.1%        20.3%        60.0%        0.0%         | 
|TERMINAL (d)       |     2/6 (33%)    1/6 (17%)    0/6 (0%)     1/8 (13%)   |1/7 (14%)    2/9 (22%)    5/9 (56%)    0/7 (0%)     | 
|FIRST INCIDENCE    |     128          288 (T)      ---          288 (T)     |288 (T)      288 (T)      125          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.144N     P=0.319N     P=0.124N     P=0.222N    |P=0.443N     P=0.593      P=0.075      P=0.500N     | 
|POLY 3             |     P=0.154N     P=0.385N     P=0.094N     P=0.265N    |P=0.423N     P=0.590      P=0.057      P=0.486N     | 
|POLY 1.5           |     P=0.156N     P=0.400N     P=0.095N     P=0.280N    |P=0.400N     P=0.567      P=0.042 *    P=0.486N     | 
|POLY 6             |     P=0.152N     P=0.362N     P=0.093N     P=0.247N    |P=0.455N     P=0.602      P=0.069      P=0.490N     | 
|LOGISTIC REGRESSION|     P=0.165N     P=0.330N     P=0.107N     P=0.287N    |P=0.421N     P=0.593      P=0.031 *    (e)          | 
|COCH-ARM / FISHERS |     P=0.187N     P=0.291N     P=0.105N     P=0.291N    |P=0.424N     P=0.500      P=0.029 *    P=0.500N     | 
|ORDER RESTRICTED   |     P=0.051N     (e)          (e)          (e)         |P=0.089N     (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                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    1/10 (10%)   2/10 (20%)   0/10 (0%)   |0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/6.94       1/6.13       2/8.57       0/8.24      |0/7.66       0/9.86       1/9.08       0/8.21       | 
|POLY-3 PERCENT (g) |     0.0%         16.3%        23.3%        0.0%        |0.0%         0.0%         11.0%        0.0%         | 
|TERMINAL (d)       |     0/6 (0%)     1/6 (17%)    0/6 (0%)     0/8 (0%)    |0/7 (0%)     0/9 (0%)     1/9 (11%)    0/7 (0%)     | 
|FIRST INCIDENCE    |     ---          288 (T)      127          ---         |---          ---          288 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.561N     P=0.500      P=0.257      (e)         |P=0.697      (e)          P=0.550      (e)          | 
|POLY 3             |     P=0.542N     P=0.475      P=0.276      (e)         |P=0.683      (e)          P=0.534      (e)          | 
|POLY 1.5           |     P=0.571N     P=0.461      P=0.258      (e)         |P=0.695      (e)          P=0.524      (e)          | 
|POLY 6             |     P=0.514N     P=0.490      P=0.290      (e)         |P=0.665      (e)          P=0.542      (e)          | 
|LOGISTIC REGRESSION|     P=0.628N     P=0.500      P=0.205      (e)         |(e)          (e)          P=0.550      (e)          | 
|COCH-ARM / FISHERS |     P=0.620N     P=0.500      P=0.237      (e)         |P=0.696      (e)          P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.293N     (e)          (e)          (e)         |P=0.409      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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)        |     3/10 (30%)   4/10 (40%)   6/10 (60%)   6/10 (60%)  |3/10 (30%)   4/10 (40%)   0/10 (0%)    5/10 (50%)   | 
|POLY-3 RATE (b)    |     3/6.94       4/6.13       6/8.17       6/8.24      |3/7.66       4/9.86       0/9.08       5/9.01       | 
|POLY-3 PERCENT (g) |     43.2%        65.3%        73.4%        72.9%       |39.2%        40.6%        0.0%         55.5%        | 
|TERMINAL (d)       |     3/6 (50%)    4/6 (67%)    4/6 (67%)    6/8 (75%)   |3/7 (43%)    4/9 (44%)    0/9 (0%)     4/7 (57%)    | 
|FIRST INCIDENCE    |     288 (T)      288 (T)      226          288 (T)     |288 (T)      288 (T)      ---          168          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.282      P=0.500      P=0.207      P=0.349     |P=0.291      P=0.667      P=0.069N     P=0.342      | 
|POLY 3             |     P=0.210      P=0.405      P=0.249      P=0.255     |P=0.349      P=0.658      P=0.062N     P=0.433      | 
|POLY 1.5           |     P=0.166      P=0.361      P=0.207      P=0.211     |P=0.346      P=0.619      P=0.070N     P=0.411      | 
|POLY 6             |     P=0.260      P=0.460      P=0.306      P=0.309     |P=0.345      P=0.678N     P=0.056N     P=0.436      | 
|LOGISTIC REGRESSION|     P=0.214      P=0.500      P=0.204      P=0.349     |P=0.322      P=0.667      (e)          P=0.362      | 
|COCH-ARM / FISHERS |     P=0.109      P=0.500      P=0.185      P=0.185     |P=0.320      P=0.500      P=0.105N     P=0.325      | 
|ORDER RESTRICTED   |     P=0.169      (e)          (e)          (e)         |P=0.157      (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)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    6/10 (60%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/6.94       0/6.13       0/7.52       6/8.24      |0/7.66       0/9.86       0/9.08       0/8.21       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         72.9%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/6 (0%)     0/6 (0%)     0/6 (0%)     6/8 (75%)   |0/7 (0%)     0/9 (0%)     0/9 (0%)     0/7 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          288 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P=0.015 *   |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   (e)          (e)          P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   (e)          (e)          P=0.002 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.015 *   |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P=0.005 **  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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                                                                                                             | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    2/10 (20%)   2/10 (20%)   4/10 (40%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/6.94       2/7.01       2/7.66       4/8.24      |0/7.66       0/9.86       0/9.08       0/8.21       | 
|POLY-3 PERCENT (g) |     0.0%         28.5%        26.1%        48.6%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/6 (0%)     1/6 (17%)    1/6 (17%)    4/8 (50%)   |0/7 (0%)     0/9 (0%)     0/9 (0%)     0/7 (0%)     | 
|FIRST INCIDENCE    |     ---          143          274          288 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.078      P=0.225      P=0.257      P=0.081     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.043 *    P=0.222      P=0.245      P=0.046 *   |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.036 *    P=0.198      P=0.236      P=0.038 *   |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.051      P=0.244      P=0.254      P=0.056     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.045 *    P=0.224      P=0.244      P=0.081     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.031 *    P=0.237      P=0.237      P=0.043 *   |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.020 *    (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)        |     2/10 (20%)   0/10 (0%)    1/10 (10%)   1/10 (10%)  |1/10 (10%)   2/10 (20%)   0/10 (0%)    3/10 (30%)   | 
|POLY-3 RATE (b)    |     2/8.37       0/6.13       1/7.52       1/9.03      |1/7.66       2/9.86       0/9.08       3/8.46       | 
|POLY-3 PERCENT (g) |     23.9%        0.0%         13.3%        11.1%       |13.1%        20.3%        0.0%         35.5%        | 
|TERMINAL (d)       |     0/6 (0%)     0/6 (0%)     1/6 (17%)    0/8 (0%)    |1/7 (14%)    2/9 (22%)    0/9 (0%)     2/7 (29%)    | 
|FIRST INCIDENCE    |     127          ---          288 (T)      169         |288 (T)      288 (T)      ---          261          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.447N     P=0.297N     P=0.485N     P=0.483N    |P=0.208      P=0.593      P=0.450N     P=0.310      | 
|POLY 3             |     P=0.429N     P=0.303N     P=0.540N     P=0.472N    |P=0.237      P=0.590      P=0.466N     P=0.325      | 
|POLY 1.5           |     P=0.437N     P=0.304N     P=0.527N     P=0.486N    |P=0.238      P=0.567      P=0.476N     P=0.321      | 
|POLY 6             |     P=0.423N     P=0.298N     P=0.554N     P=0.461N    |P=0.237      P=0.602      P=0.458N     P=0.327      | 
|LOGISTIC REGRESSION|     P=0.549N     P=0.161N     P=0.521N     P=0.584N    |P=0.214      P=0.593      (e)          P=0.307      | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.237N     P=0.500N     P=0.500N    |P=0.227      P=0.500      P=0.500N     P=0.291      | 
|ORDER RESTRICTED   |     P=0.266N     (e)          (e)          (e)         |P=0.167      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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                                                                                                                            | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/10 (70%)   6/10 (60%)   8/10 (80%)   5/10 (50%)  |8/10 (80%)   9/10 (90%)   10/10 (100%) 6/10 (60%)   | 
|POLY-3 RATE (b)    |     7/9.09       6/7.01       8/9.09       5/9.03      |8/8.13       9/9.86       10/10.00     6/9.01       | 
|POLY-3 PERCENT (g) |     77.0%        85.6%        88.1%        55.4%       |98.4%        91.3%        100.0%       66.6%        | 
|TERMINAL (d)       |     4/6 (67%)    5/6 (83%)    5/6 (83%)    4/8 (50%)   |7/7 (100%)   9/9 (100%)   9/9 (100%)   5/7 (71%)    | 
|FIRST INCIDENCE    |     128          143          127          169         |233          288 (T)      125          168          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.132N     P=0.565N     P=0.521      P=0.205N    |P=0.181N     P=0.455N     P=0.735N     P=0.285N     | 
|POLY 3             |     P=0.171N     P=0.577      P=0.500      P=0.319N    |P=0.026N*    P=0.659N     P=1.000      P=0.116N     | 
|POLY 1.5           |     P=0.178N     P=0.563      P=0.500      P=0.327N    |P=0.032N*    P=0.747N     P=0.895      P=0.142N     | 
|POLY 6             |     P=0.167N     P=0.589      P=0.500      P=0.314N    |P=0.032N*    P=0.673N     P=1.000      P=0.133N     | 
|LOGISTIC REGRESSION|     P=0.174N     P=0.695      P=0.521      P=0.310N    |P=0.097N     P=0.436N     P=0.466      P=0.186N     | 
|COCH-ARM / FISHERS |     P=0.288N     P=0.500N     P=0.500      P=0.325N    |P=0.146N     P=0.500      P=0.237      P=0.314N     | 
|ORDER RESTRICTED   |     P=0.114N     (e)          (e)          (e)         |P=0.013N*    (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                                                                                                                            | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    2/10 (20%)   0/10 (0%)    0/10 (0%)   |2/10 (20%)   2/10 (20%)   1/10 (10%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/6.94       2/8.13       0/7.52       0/8.24      |2/7.66       2/9.86       1/9.08       1/8.21       | 
|POLY-3 PERCENT (g) |     0.0%         24.6%        0.0%         0.0%        |26.1%        20.3%        11.0%        12.2%        | 
|TERMINAL (d)       |     0/6 (0%)     0/6 (0%)     0/6 (0%)     0/8 (0%)    |2/7 (29%)    2/9 (22%)    1/9 (11%)    1/7 (14%)    | 
|FIRST INCIDENCE    |     ---          13           ---          ---         |288 (T)      288 (T)      288 (T)      288 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.402N     P=0.228      (e)          (e)         |P=0.338N     P=0.611N     P=0.407N     P=0.500N     | 
|POLY 3             |     P=0.342N     P=0.261      (e)          (e)         |P=0.331N     P=0.606N     P=0.438N     P=0.474N     | 
|POLY 1.5           |     P=0.368N     P=0.241      (e)          (e)         |P=0.326N     P=0.632N     P=0.456N     P=0.474N     | 
|POLY 6             |     P=0.319N     P=0.282      (e)          (e)         |P=0.336N     P=0.591N     P=0.423N     P=0.481N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.338N     P=0.611N     P=0.407N     P=0.500N     | 
|COCH-ARM / FISHERS |     P=0.403N     P=0.237      (e)          (e)         |P=0.327N     P=0.709N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.226N     (e)          (e)          (e)         |P=0.383N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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)        |     0/10 (0%)    0/10 (0%)    2/10 (20%)   0/10 (0%)   |0/10 (0%)    2/10 (20%)   8/10 (80%)   5/10 (50%)   | 
|POLY-3 RATE (b)    |     0/6.94       0/6.13       2/7.66       0/8.24      |0/7.66       2/9.86       8/10.00      5/8.21       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         26.1%        0.0%        |0.0%         20.3%        80.0%        60.9%        | 
|TERMINAL (d)       |     0/6 (0%)     0/6 (0%)     1/6 (17%)    0/8 (0%)    |0/7 (0%)     2/9 (22%)    7/9 (78%)    5/7 (71%)    | 
|FIRST INCIDENCE    |     ---          ---          274          ---         |---          288 (T)      125          288 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.653      (e)          P=0.257      (e)         |P=0.004 **   P=0.290      P=0.004 **   P=0.016 *    | 
|POLY 3             |     P=0.708N     (e)          P=0.245      (e)         |P<0.001 **   P=0.290      P<0.001 **   P=0.007 **   | 
|POLY 1.5           |     P=0.684      (e)          P=0.236      (e)         |P=0.002 **   P=0.272      P<0.001 **   P=0.008 **   | 
|POLY 6             |     P=0.692N     (e)          P=0.254      (e)         |P<0.001 **   P=0.299      P<0.001 **   P=0.005 **   | 
|LOGISTIC REGRESSION|     P=0.645      (e)          P=0.244      (e)         |P=0.008 **   P=0.290      P<0.001 **   P=0.016 *    | 
|COCH-ARM / FISHERS |     P=0.597      (e)          P=0.237      (e)         |P=0.009 **   P=0.237      P<0.001 **   P=0.016 *    | 
|ORDER RESTRICTED   |     P=0.247      (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)        |     6/10 (60%)   3/10 (30%)   7/10 (70%)   7/10 (70%)  |6/10 (60%)   9/10 (90%)   10/10 (100%) 9/10 (90%)   | 
|POLY-3 RATE (b)    |     6/7.66       3/6.13       7/8.57       7/8.24      |6/9.08       9/9.86       10/10.00     9/9.27       | 
|POLY-3 PERCENT (g) |     78.4%        48.9%        81.7%        85.0%       |66.1%        91.3%        100.0%       97.1%        | 
|TERMINAL (d)       |     5/6 (83%)    3/6 (50%)    5/6 (83%)    7/8 (88%)   |4/7 (57%)    9/9 (100%)   9/9 (100%)   7/7 (100%)   | 
|FIRST INCIDENCE    |     189          288 (T)      127          288 (T)     |102          288 (T)      125          168          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.494      P=0.173N     P=0.514      P=0.568N    |P=0.093      P=0.451      P=0.296      P=0.238      | 
|POLY 3             |     P=0.334      P=0.282N     P=0.683      P=0.626     |P=0.046 *    P=0.213      P=0.068      P=0.115      | 
|POLY 1.5           |     P=0.309      P=0.315N     P=0.622      P=0.565     |P=0.060      P=0.198      P=0.053      P=0.130      | 
|POLY 6             |     P=0.360      P=0.246N     P=0.721      P=0.684     |P=0.033 *    P=0.202      P=0.075      P=0.100      | 
|LOGISTIC REGRESSION|     P=0.367      P=0.223N     P=0.568      P=0.739N    |P=0.103      P=0.194      P=0.051      P=0.175      | 
|COCH-ARM / FISHERS |     P=0.209      P=0.185N     P=0.500      P=0.500     |P=0.089      P=0.152      P=0.043 *    P=0.152      | 
|ORDER RESTRICTED   |     P=0.267      (e)          (e)          (e)         |P=0.011 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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                                                                                                                | 
|     Vacuolization Cytoplasmic Diffuse                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    2/10 (20%)   0/10 (0%)    0/10 (0%)   |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/6.94       2/6.13       0/7.52       0/8.24      |0/7.66       0/9.86       0/9.08       0/8.21       | 
|POLY-3 PERCENT (g) |     0.0%         32.6%        0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/6 (0%)     2/6 (33%)    0/6 (0%)     0/8 (0%)    |0/7 (0%)     0/9 (0%)     0/9 (0%)     0/7 (0%)     | 
|FIRST INCIDENCE    |     ---          288 (T)      ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.346N     P=0.229      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.388N     P=0.189      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.412N     P=0.176      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.363N     P=0.205      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.229      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.403N     P=0.237      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.164N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   1/10 (10%)   2/10 (20%)   0/10 (0%)   |0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     1/7.66       1/7.13       2/8.43       0/8.24      |0/7.66       0/9.86       0/9.08       1/8.46       | 
|POLY-3 PERCENT (g) |     13.1%        14.0%        23.7%        0.0%        |0.0%         0.0%         0.0%         11.8%        | 
|TERMINAL (d)       |     0/6 (0%)     0/6 (0%)     1/6 (17%)    0/8 (0%)    |0/7 (0%)     0/9 (0%)     0/9 (0%)     0/7 (0%)     | 
|FIRST INCIDENCE    |     189          13           127          ---         |---          ---          ---          261          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.343N     P=0.729      P=0.500      P=0.500N    |P=0.191      (e)          (e)          P=0.527      | 
|POLY 3             |     P=0.326N     P=0.749      P=0.535      P=0.485N    |P=0.196      (e)          (e)          P=0.520      | 
|POLY 1.5           |     P=0.335N     P=0.740      P=0.527      P=0.492N    |P=0.198      (e)          (e)          P=0.517      | 
|POLY 6             |     P=0.319N     P=0.758      P=0.536      P=0.479N    |P=0.194      (e)          (e)          P=0.521      | 
|LOGISTIC REGRESSION|     P=0.467N     P=0.574N     P=0.471      P=0.527N    |P=0.196      (e)          (e)          P=0.505      | 
|COCH-ARM / FISHERS |     P=0.361N     P=0.763N     P=0.500      P=0.500N    |P=0.196      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.247N     (e)          (e)          (e)         |P=0.138      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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: Perivascular                                                                                                               | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    1/10 (10%)   1/10 (10%)   0/10 (0%)   |2/10 (20%)   0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/6.94       1/6.13       1/7.52       0/8.24      |2/7.66       0/9.86       0/9.08       1/8.21       | 
|POLY-3 PERCENT (g) |     0.0%         16.3%        13.3%        0.0%        |26.1%        0.0%         0.0%         12.2%        | 
|TERMINAL (d)       |     0/6 (0%)     1/6 (17%)    1/6 (17%)    0/8 (0%)    |2/7 (29%)    0/9 (0%)     0/9 (0%)     1/7 (14%)    | 
|FIRST INCIDENCE    |     ---          288 (T)      288 (T)      ---         |288 (T)      ---          ---          288 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.529N     P=0.500      P=0.500      (e)         |P=0.473N     P=0.178N     P=0.178N     P=0.500N     | 
|POLY 3             |     P=0.551N     P=0.475      P=0.516      (e)         |P=0.500N     P=0.169N     P=0.185N     P=0.474N     | 
|POLY 1.5           |     P=0.573N     P=0.461      P=0.510      (e)         |P=0.490N     P=0.183N     P=0.196N     P=0.474N     | 
|POLY 6             |     P=0.529N     P=0.490      P=0.520      (e)         |P=0.502N     P=0.162N     P=0.176N     P=0.481N     | 
|LOGISTIC REGRESSION|     (e)          P=0.500      P=0.500      (e)         |P=0.473N     (e)          (e)          P=0.500N     | 
|COCH-ARM / FISHERS |     P=0.597N     P=0.500      P=0.500      (e)         |P=0.460N     P=0.237N     P=0.237N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.364N     (e)          (e)          (e)         |P=0.094N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Infiltration Cellular Plasma Cell                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   0/9 (0%)     2/9 (22%)    1/10 (10%)  |2/10 (20%)   1/10 (10%)   0/10 (0%)    2/9 (22%)    | 
|POLY-3 RATE (b)    |     1/6.94       0/6.12       2/7.95       1/8.24      |2/8.57       1/9.86       0/9.08       2/8.74       | 
|POLY-3 PERCENT (g) |     14.4%        0.0%         25.2%        12.1%       |23.3%        10.1%        0.0%         22.9%        | 
|TERMINAL (d)       |     1/6 (17%)    0/6 (0%)     1/6 (17%)    1/8 (13%)   |1/7 (14%)    1/9 (11%)    0/9 (0%)     1/7 (14%)    | 
|FIRST INCIDENCE    |     288 (T)      ---          226          288 (T)     |126          288 (T)      ---          185          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.584      P=0.500N     P=0.516      P=0.702N    |P=0.584      P=0.429N     P=0.212N     P=0.684N     | 
|POLY 3             |     P=0.595      P=0.525N     P=0.550      P=0.725N    |P=0.568      P=0.449N     P=0.211N     P=0.698N     | 
|POLY 1.5           |     P=0.575      P=0.541N     P=0.519      P=0.741N    |P=0.566      P=0.462N     P=0.216N     P=0.702      | 
|POLY 6             |     P=0.612      P=0.510N     P=0.574      P=0.708N    |P=0.568      P=0.441N     P=0.205N     P=0.694N     | 
|LOGISTIC REGRESSION|     P=0.555      (e)          P=0.500      P=0.702N    |P=0.457      P=0.695N     P=0.292N     P=0.533      | 
|COCH-ARM / FISHERS |     P=0.507      P=0.526N     P=0.458      P=0.763N    |P=0.560      P=0.500N     P=0.237N     P=0.667      | 
|ORDER RESTRICTED   |     P=0.431      (e)          (e)          (e)         |P=0.371N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/10 (10%)   0/10 (0%)    3/10 (30%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |                                                        |1/7.66       0/9.86       3/9.08       1/8.46       | 
|POLY-3 PERCENT (g) |                                                        |13.1%        0.0%         33.0%        11.8%        | 
|TERMINAL (d)       |                                                        |1/7 (14%)    0/9 (0%)     3/9 (33%)    0/7 (0%)     | 
|FIRST INCIDENCE    |                                                        |288 (T)      ---          288 (T)      261          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.452      P=0.450N     P=0.389      P=0.746N     | 
|POLY 3             |                                                        |P=0.450      P=0.450N     P=0.357      P=0.741N     | 
|POLY 1.5           |                                                        |P=0.463      P=0.463N     P=0.336      P=0.744N     | 
|POLY 6             |                                                        |P=0.440      P=0.443N     P=0.374      P=0.740N     | 
|LOGISTIC REGRESSION|                                                        |P=0.465      (e)          P=0.389      P=0.760N     | 
|COCH-ARM / FISHERS |                                                        |P=0.468      P=0.500N     P=0.291      P=0.763N     | 
|ORDER RESTRICTED   |                                                        |P=0.273      (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)        |     1/10 (10%)   1/10 (10%)   0/10 (0%)    1/10 (10%)  |2/10 (20%)   1/10 (10%)   1/10 (10%)   0/10 (0%)    | 
|POLY-3 RATE (b)    |     1/6.94       1/6.13       0/7.52       1/9.03      |2/8.13       1/9.86       1/9.08       0/8.21       | 
|POLY-3 PERCENT (g) |     14.4%        16.3%        0.0%         11.1%       |24.6%        10.1%        11.0%        0.0%         | 
|TERMINAL (d)       |     1/6 (17%)    1/6 (17%)    0/6 (0%)     0/8 (0%)    |1/7 (14%)    1/9 (11%)    1/9 (11%)    0/7 (0%)     | 
|FIRST INCIDENCE    |     288 (T)      288 (T)      ---          169         |233          288 (T)      288 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.543N     P=0.771      P=0.500N     P=0.715N    |P=0.147N     P=0.415N     P=0.427N     P=0.240N     | 
|POLY 3             |     P=0.581N     P=0.739      P=0.484N     P=0.701N    |P=0.158N     P=0.430N     P=0.460N     P=0.220N     | 
|POLY 1.5           |     P=0.593N     P=0.721      P=0.490N     P=0.726N    |P=0.152N     P=0.444N     P=0.468N     P=0.215N     | 
|POLY 6             |     P=0.570N     P=0.757      P=0.480N     P=0.678N    |P=0.164N     P=0.429N     P=0.457N     P=0.233N     | 
|LOGISTIC REGRESSION|     P=0.603N     P=0.771      (e)          P=0.759     |P=0.138N     P=0.486N     P=0.475N     P=0.222N     | 
|COCH-ARM / FISHERS |     P=0.620N     P=0.763N     P=0.500N     P=0.763N    |P=0.143N     P=0.500N     P=0.500N     P=0.237N     | 
|ORDER RESTRICTED   |     P=0.434N     (e)          (e)          (e)         |P=0.106N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pleura                                                                                                                           | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     3/3 (100%)   0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|POLY-3 RATE (b)    |     0/0.00       3/3.00       0/0.00       0/0.00      |0/0.00       0/0.00       0/0.00       0/0.00       | 
|POLY-3 PERCENT (g) |     0.0%         100.0%       0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          13           ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/5 (0%)     1/6 (17%)    2/5 (40%)    4/7 (57%)   |1/6 (17%)    3/5 (60%)    0/7 (0%)     2/7 (29%)    | 
|POLY-3 RATE (b)    |     0/5.00       1/6.00       2/4.34       4/7.00      |1/6.00       3/5.00       0/6.08       2/6.74       | 
|POLY-3 PERCENT (g) |     0.0%         16.7%        46.0%        57.1%       |16.7%        60.0%        0.0%         29.7%        | 
|TERMINAL (d)       |     0/5 (0%)     1/6 (17%)    2/3 (67%)    4/7 (57%)   |1/6 (17%)    3/5 (60%)    0/6 (0%)     2/6 (33%)    | 
|FIRST INCIDENCE    |     ---          288 (T)      288 (T)      288 (T)     |288 (T)      288 (T)      ---          288 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.030 *    P=0.536      P=0.118      P=0.083     |P=0.585      P=0.207      P=0.500N     P=0.500      | 
|POLY 3             |     P=0.019 *    P=0.536      P=0.166      P=0.049 *   |P=0.614N     P=0.193      P=0.497N     P=0.543      | 
|POLY 1.5           |     P=0.020 *    P=0.536      P=0.183      P=0.049 *   |P=0.606N     P=0.193      P=0.491N     P=0.549      | 
|POLY 6             |     P=0.018 *    P=0.536      P=0.142      P=0.049 *   |P=0.625N     P=0.193      P=0.500N     P=0.533      | 
|LOGISTIC REGRESSION|     (e)          P=0.536      P=0.118      P=0.083     |P=0.585      P=0.207      (e)          P=0.500      | 
|COCH-ARM / FISHERS |     P=0.025 *    P=0.545      P=0.222      P=0.071     |P=0.589N     P=0.197      P=0.462N     P=0.563      | 
|ORDER RESTRICTED   |     P=0.018 *    (e)          (e)          (e)         |P=0.292N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)   |2/10 (20%)   0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/6.94       1/7.13       0/7.52       0/8.24      |2/9.53       0/9.86       0/9.08       1/9.01       | 
|POLY-3 PERCENT (g) |     0.0%         14.0%        0.0%         0.0%        |21.0%        0.0%         0.0%         11.1%        | 
|TERMINAL (d)       |     0/6 (0%)     0/6 (0%)     0/6 (0%)     0/8 (0%)    |0/7 (0%)     0/9 (0%)     0/9 (0%)     0/7 (0%)     | 
|FIRST INCIDENCE    |     ---          14           ---          ---         |102          ---          ---          168          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.561N     P=0.479      (e)          (e)         |P=0.442N     P=0.228N     P=0.240N     P=0.462N     | 
|POLY 3             |     P=0.553N     P=0.505      (e)          (e)         |P=0.468N     P=0.218N     P=0.237N     P=0.520N     | 
|POLY 1.5           |     P=0.567N     P=0.490      (e)          (e)         |P=0.466N     P=0.221N     P=0.237N     P=0.513N     | 
|POLY 6             |     P=0.538N     P=0.521      (e)          (e)         |P=0.468N     P=0.214N     P=0.232N     P=0.527N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.659      (e)          P=0.466N     (e)          | 
|COCH-ARM / FISHERS |     P=0.568N     P=0.500      (e)          (e)         |P=0.460N     P=0.237N     P=0.237N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.356N     (e)          (e)          (e)         |P=0.131N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/10 (40%)   0/10 (0%)    2/10 (20%)   1/10 (10%)  |1/10 (10%)   2/10 (20%)   0/10 (0%)    5/10 (50%)   | 
|POLY-3 RATE (b)    |     4/9.28       0/6.13       2/7.52       1/9.03      |1/7.66       2/9.86       0/9.08       5/9.20       | 
|POLY-3 PERCENT (g) |     43.1%        0.0%         26.6%        11.1%       |13.1%        20.3%        0.0%         54.4%        | 
|TERMINAL (d)       |     1/6 (17%)    0/6 (0%)     2/6 (33%)    0/8 (0%)    |1/7 (14%)    2/9 (22%)    0/9 (0%)     3/7 (43%)    | 
|FIRST INCIDENCE    |     127          ---          288 (T)      169         |288 (T)      288 (T)      ---          185          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.155N     P=0.093N     P=0.333N     P=0.160N    |P=0.028 *    P=0.593      P=0.450N     P=0.101      | 
|POLY 3             |     P=0.117N     P=0.097N     P=0.428N     P=0.152N    |P=0.026 *    P=0.590      P=0.466N     P=0.098      | 
|POLY 1.5           |     P=0.122N     P=0.092N     P=0.393N     P=0.156N    |P=0.025 *    P=0.567      P=0.476N     P=0.086      | 
|POLY 6             |     P=0.113N     P=0.096N     P=0.457N     P=0.146N    |P=0.027 *    P=0.602      P=0.458N     P=0.107      | 
|LOGISTIC REGRESSION|     P=0.199N     P=0.027N*    P=0.330N     P=0.183N    |P=0.030 *    P=0.593      (e)          P=0.078      | 
|COCH-ARM / FISHERS |     P=0.180N     P=0.043N*    P=0.314N     P=0.152N    |P=0.031 *    P=0.500      P=0.500N     P=0.070      | 
|ORDER RESTRICTED   |     P=0.051N     (e)          (e)          (e)         |P=0.019 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Hyperkeratosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   0/10 (0%)    3/10 (30%)   2/10 (20%)  |1/10 (10%)   2/10 (20%)   4/10 (40%)   4/10 (40%)   | 
|POLY-3 RATE (b)    |     2/6.94       0/6.13       3/7.52       2/8.24      |1/8.57       2/9.86       4/9.08       4/8.94       | 
|POLY-3 PERCENT (g) |     28.8%        0.0%         39.9%        24.3%       |11.7%        20.3%        44.0%        44.7%        | 
|TERMINAL (d)       |     2/6 (33%)    0/6 (0%)     3/6 (50%)    2/8 (25%)   |0/7 (0%)     2/9 (22%)    4/9 (44%)    3/7 (43%)    | 
|FIRST INCIDENCE    |     288 (T)      ---          288 (T)      288 (T)     |126          288 (T)      288 (T)      185          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.552      P=0.229N     P=0.500      P=0.597N    |P=0.076      P=0.571      P=0.231      P=0.188      | 
|POLY 3             |     P=0.553      P=0.249N     P=0.543      P=0.643N    |P=0.080      P=0.550      P=0.161      P=0.154      | 
|POLY 1.5           |     P=0.527      P=0.269N     P=0.526      P=0.671N    |P=0.084      P=0.538      P=0.155      P=0.155      | 
|POLY 6             |     P=0.574      P=0.230N     P=0.554      P=0.615N    |P=0.076      P=0.558      P=0.169      P=0.150      | 
|LOGISTIC REGRESSION|     P=0.552      (e)          P=0.500      P=0.597N    |P=0.083      P=0.305      P=0.138      P=0.114      | 
|COCH-ARM / FISHERS |     P=0.416      P=0.237N     P=0.500      P=0.709N    |P=0.084      P=0.500      P=0.152      P=0.152      | 
|ORDER RESTRICTED   |     P=0.359      (e)          (e)          (e)         |P=0.106      (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)        |     2/10 (20%)   0/10 (0%)    3/10 (30%)   2/10 (20%)  |1/10 (10%)   2/10 (20%)   4/10 (40%)   4/10 (40%)   | 
|POLY-3 RATE (b)    |     2/6.94       0/6.13       3/7.52       2/8.24      |1/7.66       2/9.86       4/9.08       4/8.94       | 
|POLY-3 PERCENT (g) |     28.8%        0.0%         39.9%        24.3%       |13.1%        20.3%        44.0%        44.7%        | 
|TERMINAL (d)       |     2/6 (33%)    0/6 (0%)     3/6 (50%)    2/8 (25%)   |1/7 (14%)    2/9 (22%)    4/9 (44%)    3/7 (43%)    | 
|FIRST INCIDENCE    |     288 (T)      ---          288 (T)      288 (T)     |288 (T)      288 (T)      288 (T)      185          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.552      P=0.229N     P=0.500      P=0.597N    |P=0.066      P=0.593      P=0.235      P=0.168      | 
|POLY 3             |     P=0.553      P=0.249N     P=0.543      P=0.643N    |P=0.102      P=0.590      P=0.200      P=0.193      | 
|POLY 1.5           |     P=0.527      P=0.269N     P=0.526      P=0.671N    |P=0.101      P=0.567      P=0.182      P=0.183      | 
|POLY 6             |     P=0.574      P=0.230N     P=0.554      P=0.615N    |P=0.099      P=0.602      P=0.216      P=0.194      | 
|LOGISTIC REGRESSION|     P=0.552      (e)          P=0.500      P=0.597N    |P=0.081      P=0.593      P=0.235      P=0.163      | 
|COCH-ARM / FISHERS |     P=0.416      P=0.237N     P=0.500      P=0.709N    |P=0.084      P=0.500      P=0.152      P=0.152      | 
|ORDER RESTRICTED   |     P=0.359      (e)          (e)          (e)         |P=0.142      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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)        |     2/10 (20%)   1/10 (10%)   0/10 (0%)    1/10 (10%)  |                                                    | 
|POLY-3 RATE (b)    |     2/7.85       1/6.13       0/7.52       1/8.24      |                                                    | 
|POLY-3 PERCENT (g) |     25.5%        16.3%        0.0%         12.1%       |                                                    | 
|TERMINAL (d)       |     1/6 (17%)    1/6 (17%)    0/6 (0%)     1/8 (13%)   |                                                    | 
|FIRST INCIDENCE    |     127          288 (T)      ---          288 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.304N     P=0.542N     P=0.240N     P=0.445N    |                                                    | 
|POLY 3             |     P=0.337N     P=0.591N     P=0.232N     P=0.482N    |                                                    | 
|POLY 1.5           |     P=0.339N     P=0.600N     P=0.232N     P=0.495N    |                                                    | 
|POLY 6             |     P=0.334N     P=0.573N     P=0.231N     P=0.465N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.343N     P=0.527N     P=0.238N     P=0.519N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.361N     P=0.500N     P=0.237N     P=0.500N    |                                                    | 
|ORDER RESTRICTED   |     P=0.197N     (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)        |     3/9 (33%)    3/10 (30%)   3/10 (30%)   2/10 (20%)  |2/10 (20%)   1/10 (10%)   0/10 (0%)    4/9 (44%)    | 
|POLY-3 RATE (b)    |     3/6.46       3/9.12       3/8.03       2/9.20      |2/9.53       1/10.00      0/9.08       4/8.74       | 
|POLY-3 PERCENT (g) |     46.5%        32.9%        37.4%        21.7%       |21.0%        10.0%        0.0%         45.7%        | 
|TERMINAL (d)       |     3/6 (50%)    0/6 (0%)     2/6 (33%)    1/8 (13%)   |0/7 (0%)     0/9 (0%)     0/9 (0%)     2/6 (33%)    | 
|FIRST INCIDENCE    |     288 (T)      13           226          93          |102          274          ---          168          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.293N     P=0.640      P=0.663N     P=0.388N    |P=0.153      P=0.447N     P=0.240N     P=0.350      | 
|POLY 3             |     P=0.262N     P=0.495N     P=0.571N     P=0.322N    |P=0.101      P=0.483N     P=0.237N     P=0.268      | 
|POLY 1.5           |     P=0.281N     P=0.537N     P=0.593N     P=0.357N    |P=0.102      P=0.490N     P=0.237N     P=0.266      | 
|POLY 6             |     P=0.254N     P=0.468N     P=0.558N     P=0.303N    |P=0.099      P=0.473N     P=0.232N     P=0.269      | 
|LOGISTIC REGRESSION|     P=0.438N     P=0.460N     P=0.613N     P=0.446N    |P=0.071      P=0.436      P=0.466N     P=0.135      | 
|COCH-ARM / FISHERS |     P=0.337N     P=0.630N     P=0.630N     P=0.444N    |P=0.116      P=0.500N     P=0.237N     P=0.259      | 
|ORDER RESTRICTED   |     P=0.277N     (e)          (e)          (e)         |P=0.033 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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)        |     4/9 (44%)    2/10 (20%)   2/10 (20%)   3/10 (30%)  |3/10 (30%)   2/10 (20%)   5/10 (50%)   3/9 (33%)    | 
|POLY-3 RATE (b)    |     4/7.37       2/6.13       2/7.52       3/8.24      |3/8.13       2/9.86       5/10.00      3/7.21       | 
|POLY-3 PERCENT (g) |     54.3%        32.6%        26.6%        36.4%       |36.9%        20.3%        50.0%        41.6%        | 
|TERMINAL (d)       |     3/6 (50%)    2/6 (33%)    2/6 (33%)    3/8 (38%)   |2/7 (29%)    2/9 (22%)    4/9 (44%)    3/6 (50%)    | 
|FIRST INCIDENCE    |     128          288 (T)      288 (T)      288 (T)     |233          288 (T)      125          288 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.315N     P=0.334N     P=0.323N     P=0.345N    |P=0.370      P=0.382N     P=0.477      P=0.616      | 
|POLY 3             |     P=0.359N     P=0.406N     P=0.288N     P=0.424N    |P=0.345      P=0.404N     P=0.469      P=0.626      | 
|POLY 1.5           |     P=0.364N     P=0.413N     P=0.277N     P=0.433N    |P=0.382      P=0.423N     P=0.437      P=0.645      | 
|POLY 6             |     P=0.356N     P=0.393N     P=0.305N     P=0.413N    |P=0.305      P=0.402N     P=0.479      P=0.590      | 
|LOGISTIC REGRESSION|     P=0.329N     P=0.330N     P=0.242N     P=0.390N    |P=0.409      P=0.424N     P=0.325      P=0.662      | 
|COCH-ARM / FISHERS |     P=0.429N     P=0.259N     P=0.259N     P=0.430N    |P=0.408      P=0.500N     P=0.325      P=0.630      | 
|ORDER RESTRICTED   |     P=0.282N     (e)          (e)          (e)         |P=0.389      (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                                                                                                                    | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   0/10 (0%)    1/10 (10%)   1/10 (10%)  |2/10 (20%)   5/10 (50%)   2/10 (20%)   2/10 (20%)   | 
|POLY-3 RATE (b)    |     2/7.46       0/6.13       1/7.52       1/8.24      |2/8.13       5/9.86       2/9.08       2/9.20       | 
|POLY-3 PERCENT (g) |     26.8%        0.0%         13.3%        12.1%       |24.6%        50.7%        22.0%        21.7%        | 
|TERMINAL (d)       |     1/6 (17%)    0/6 (0%)     1/6 (17%)    1/8 (13%)   |1/7 (14%)    5/9 (56%)    2/9 (22%)    0/7 (0%)     | 
|FIRST INCIDENCE    |     226          ---          288 (T)      288 (T)     |233          288 (T)      288 (T)      185          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.416N     P=0.257N     P=0.484N     P=0.417N    |P=0.407N     P=0.304      P=0.618N     P=0.669N     | 
|POLY 3             |     P=0.441N     P=0.270N     P=0.497N     P=0.463N    |P=0.320N     P=0.265      P=0.663N     P=0.658N     | 
|POLY 1.5           |     P=0.444N     P=0.280N     P=0.496N     P=0.477N    |P=0.328N     P=0.245      P=0.672N     P=0.665N     | 
|POLY 6             |     P=0.441N     P=0.261N     P=0.506N     P=0.454N    |P=0.321N     P=0.266      P=0.661N     P=0.659N     | 
|LOGISTIC REGRESSION|     P=0.442N     P=0.255N     P=0.480N     P=0.466N    |P=0.378N     P=0.252      P=0.677N     P=0.689      | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.237N     P=0.500N     P=0.500N    |P=0.382N     P=0.175      P=0.709N     P=0.709N     | 
|ORDER RESTRICTED   |     P=0.241N     (e)          (e)          (e)         |P=0.362N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/04/03                           EXPERIMENT: 97013 TEST: 97                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 42 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: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |7/10 (70%)   10/10 (100%) 9/10 (90%)   8/10 (80%)   | 
|POLY-3 RATE (b)    |                                                        |7/7.66       10/10.00     9/9.08       8/8.46       | 
|POLY-3 PERCENT (g) |                                                        |91.4%        100.0%       99.1%        94.5%        | 
|TERMINAL (d)       |                                                        |7/7 (100%)   9/9 (100%)   9/9 (100%)   7/7 (100%)   | 
|FIRST INCIDENCE    |                                                        |288 (T)      274          288 (T)      261          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.393      P=0.571      P=1.000      P=0.527      | 
|POLY 3             |                                                        |P=0.851N     P=0.680      P=0.740      P=0.865      | 
|POLY 1.5           |                                                        |P=0.691N     P=0.330      P=0.485      P=0.719      | 
|POLY 6             |                                                        |P=0.963      P=0.988      P=0.990      P=0.994      | 
|LOGISTIC REGRESSION|                                                        |P=0.393      (e)          P=1.000      (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.559      P=0.105      P=0.291      P=0.500      | 
|ORDER RESTRICTED   |                                                        |P=0.194      (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).