National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/20473

TDMS Study 97013-06 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 06/11/04       
EXPERIMENT: 97013 TEST: 06                                                                                     TIME: 08:41:37       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-65406                              ROUTE: SKIN APPLICATION                                        NTP C#: 97013F       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                            FINAL#1 MICE                                                            
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE 001    0 MG/KG                                                                       
                                       INCLUDE 002    0 MG/KG                                                                       
                                       INCLUDE 003    64 MG/KG                                                                      
                                       INCLUDE 004    64 MG/KG                                                                      
                                       INCLUDE 005    128     MG/KG                                                                 
                                       INCLUDE 006    128     MG/KG                                                                 
                                       INCLUDE 007    256     MG/KG                                                                 
                                       INCLUDE 008    256     MG/KG                                                                 
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 06/11/04       
EXPERIMENT: 97013 TEST: 06                                                                                     TIME: 08:41:37       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-65406                              ROUTE: SKIN APPLICATION                                        NTP C#: 97013F       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF     WATER DISINFECTION MODEL (BROMODICHLOR                                                                       
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Kidney                                 Nephropathy                                                                                  
Kidney: Renal Tubule                   Hypertrophy                                                                                  
===============================================================                                                                     
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMO
DICHLOR                                                                                                                             
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/15 (60%)   9/15 (60%)   6/15 (40%)   8/15 (53%)  |0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     9/13.69      9/15.00      6/15.00      8/13.85     |0/12.19      0/12.21      0/12.88      0/11.87      | 
|POLY-3 PERCENT (g) |     65.7%        60.0%        40.0%        57.8%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     9/13 (69%)   8/14 (57%)   6/15 (40%)   8/13 (62%)  |0/11 (0%)    0/10 (0%)    0/12 (0%)    0/10 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      133          183 (T)      183 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.369N     P=0.549N     P=0.126N     P=0.500N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.367N     P=0.527N     P=0.157N     P=0.485N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.365N     P=0.571N     P=0.183N     P=0.490N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.372N     P=0.484N     P=0.134N     P=0.484N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.353N     P=0.599N     P=0.126N     P=0.500N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.363N     P=0.645N     P=0.233N     P=0.500N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.298N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    0/15 (0%)    2/15 (13%)  |8/15 (53%)   8/15 (53%)   11/15 (73%)  5/15 (33%)   | 
|POLY-3 RATE (b)    |     1/13.69      1/14.38      0/15.00      2/13.85     |8/13.41      8/12.97      11/15.00     5/12.81      | 
|POLY-3 PERCENT (g) |     7.3%         7.0%         0.0%         14.4%       |59.7%        61.7%        73.3%        39.0%        | 
|TERMINAL (d)       |     1/13 (8%)    1/14 (7%)    0/15 (0%)    2/13 (15%)  |6/11 (55%)   6/10 (60%)   8/12 (67%)   4/10 (40%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      ---          183 (T)     |93           126          110          71           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.358      P=0.748N     P=0.471N     P=0.500     |P=0.250N     P=0.554      P=0.356      P=0.306N     | 
|POLY 3             |     P=0.367      P=0.750N     P=0.482N     P=0.504     |P=0.197N     P=0.614      P=0.357      P=0.251N     | 
|POLY 1.5           |     P=0.367      P=0.754N     P=0.489N     P=0.503     |P=0.180N     P=0.633      P=0.315      P=0.232N     | 
|POLY 6             |     P=0.368      P=0.747N     P=0.475N     P=0.504     |P=0.235N     P=0.588      P=0.387      P=0.290N     | 
|LOGISTIC REGRESSION|     P=0.358      P=0.748N     (e)          P=0.500     |P=0.192N     P=0.634N     P=0.221      P=0.231N     | 
|COCH-ARM / FISHERS |     P=0.363      P=0.759N     P=0.500N     P=0.500     |P=0.191N     P=0.642N     P=0.225      P=0.231N     | 
|ORDER RESTRICTED   |     P=0.261      (e)          (e)          (e)         |P=0.132N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Casts Protein                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/15 (20%)   1/15 (7%)    0/15 (0%)    2/15 (13%)  |6/15 (40%)   5/15 (33%)   5/15 (33%)   4/15 (27%)   | 
|POLY-3 RATE (b)    |     3/14.46      1/14.38      0/15.00      2/13.85     |6/13.07      5/12.29      5/13.66      4/13.00      | 
|POLY-3 PERCENT (g) |     20.8%        7.0%         0.0%         14.4%       |45.9%        40.7%        36.6%        30.8%        | 
|TERMINAL (d)       |     2/13 (15%)   1/14 (7%)    0/15 (0%)    2/13 (15%)  |5/11 (46%)   4/10 (40%)   4/12 (33%)   2/10 (20%)   | 
|FIRST INCIDENCE    |     113          183 (T)      ---          183 (T)     |93           179          110          105          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.445N     P=0.283N     P=0.105N     P=0.500N    |P=0.325N     P=0.558N     P=0.429N     P=0.401N     | 
|POLY 3             |     P=0.440N     P=0.299N     P=0.099N     P=0.521N    |P=0.270N     P=0.553N     P=0.462N     P=0.349N     | 
|POLY 1.5           |     P=0.441N     P=0.299N     P=0.102N     P=0.513N    |P=0.278N     P=0.528N     P=0.470N     P=0.349N     | 
|POLY 6             |     P=0.438N     P=0.299N     P=0.096N     P=0.527N    |P=0.264N     P=0.575N     P=0.456N     P=0.350N     | 
|LOGISTIC REGRESSION|     P=0.449N     P=0.361N     P=0.231N     P=0.510N    |P=0.291N     P=0.493N     P=0.497N     P=0.349N     | 
|COCH-ARM / FISHERS |     P=0.442N     P=0.299N     P=0.112N     P=0.500N    |P=0.289N     P=0.500N     P=0.500N     P=0.350N     | 
|ORDER RESTRICTED   |     P=0.181N     (e)          (e)          (e)         |P=0.343N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    0/15 (0%)    0/15 (0%)    1/15 (7%)   |2/15 (13%)   2/15 (13%)   0/15 (0%)    1/15 (7%)    | 
|POLY-3 RATE (b)    |     1/13.69      0/14.38      0/15.00      1/13.85     |2/12.19      2/12.21      0/12.88      1/11.87      | 
|POLY-3 PERCENT (g) |     7.3%         0.0%         0.0%         7.2%        |16.4%        16.4%        0.0%         8.4%         | 
|TERMINAL (d)       |     1/13 (8%)    0/14 (0%)    0/15 (0%)    1/13 (8%)   |2/11 (18%)   2/10 (20%)   0/12 (0%)    1/10 (10%)   | 
|FIRST INCIDENCE    |     183 (T)      ---          ---          183 (T)     |184 (T)      184 (T)      ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.596      P=0.485N     P=0.471N     P=0.765     |P=0.302N     P=0.670      P=0.216N     P=0.535N     | 
|POLY 3             |     P=0.591      P=0.490N     P=0.482N     P=0.759N    |P=0.288N     P=0.702N     P=0.217N     P=0.510N     | 
|POLY 1.5           |     P=0.592      P=0.494N     P=0.489N     P=0.759N    |P=0.289N     P=0.697N     P=0.219N     P=0.504N     | 
|POLY 6             |     P=0.590      P=0.487N     P=0.475N     P=0.759N    |P=0.289N     P=0.697      P=0.216N     P=0.520N     | 
|LOGISTIC REGRESSION|     P=0.596      (e)          (e)          P=0.765     |P=0.302N     P=0.670      (e)          P=0.535N     | 
|COCH-ARM / FISHERS |     P=0.596      P=0.500N     P=0.500N     P=0.759N    |P=0.290N     P=0.701N     P=0.241N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.390N     (e)          (e)          (e)         |P=0.258N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/15 (47%)   6/15 (40%)   7/15 (47%)   6/15 (40%)  |0/15 (0%)    0/15 (0%)    2/15 (13%)   3/15 (20%)   | 
|POLY-3 RATE (b)    |     7/14.46      6/14.38      7/15.00      6/13.85     |0/12.19      0/12.21      2/12.88      3/11.87      | 
|POLY-3 PERCENT (g) |     48.4%        41.7%        46.7%        43.3%       |0.0%         0.0%         15.5%        25.3%        | 
|TERMINAL (d)       |     6/13 (46%)   6/14 (43%)   7/15 (47%)   6/13 (46%)  |0/11 (0%)    0/10 (0%)    2/12 (17%)   3/10 (30%)   | 
|FIRST INCIDENCE    |     113          183 (T)      183 (T)      183 (T)     |---          ---          184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.472N     P=0.437N     P=0.510N     P=0.500N    |P=0.019 *    (e)          P=0.254      P=0.096      | 
|POLY 3             |     P=0.500N     P=0.505N     P=0.605N     P=0.541N    |P=0.019 *    (e)          P=0.242      P=0.096      | 
|POLY 1.5           |     P=0.489N     P=0.504N     P=0.619N     P=0.526N    |P=0.020 *    (e)          P=0.241      P=0.101      | 
|POLY 6             |     P=0.510N     P=0.504N     P=0.588N     P=0.554N    |P=0.018 *    (e)          P=0.243      P=0.091      | 
|LOGISTIC REGRESSION|     P=0.461N     P=0.500N     P=0.602      P=0.496N    |(e)          (e)          P=0.254      P=0.096      | 
|COCH-ARM / FISHERS |     P=0.465N     P=0.500N     P=0.642N     P=0.500N    |P=0.024 *    (e)          P=0.241      P=0.112      | 
|ORDER RESTRICTED   |     P=0.616N     (e)          (e)          (e)         |P=0.025 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    1/15 (7%)   |0/15 (0%)    1/15 (7%)    1/15 (7%)    4/15 (27%)   | 
|POLY-3 RATE (b)    |     0/13.69      0/14.38      0/15.00      1/13.85     |0/12.19      1/12.21      1/12.88      4/11.87      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         7.2%        |0.0%         8.2%         7.8%         33.7%        | 
|TERMINAL (d)       |     0/13 (0%)    0/14 (0%)    0/15 (0%)    1/13 (8%)   |0/11 (0%)    1/10 (10%)   1/12 (8%)    4/10 (40%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          183 (T)     |---          184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.192      (e)          (e)          P=0.500     |P=0.011 *    P=0.481      P=0.517      P=0.042 *    | 
|POLY 3             |     P=0.198      (e)          (e)          P=0.502     |P=0.011 *    P=0.500      P=0.511      P=0.037 *    | 
|POLY 1.5           |     P=0.198      (e)          (e)          P=0.502     |P=0.011 *    P=0.502      P=0.509      P=0.041 *    | 
|POLY 6             |     P=0.197      (e)          (e)          P=0.502     |P=0.010 *    P=0.496      P=0.512      P=0.034 *    | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.500     |(e)          P=0.481      P=0.517      P=0.042 *    | 
|COCH-ARM / FISHERS |     P=0.197      (e)          (e)          P=0.500     |P=0.015 *    P=0.500      P=0.500      P=0.050      | 
|ORDER RESTRICTED   |     P=0.122      (e)          (e)          (e)         |P=0.006 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    0/15 (0%)    1/15 (7%)   |1/15 (7%)    1/15 (7%)    1/15 (7%)    3/15 (20%)   | 
|POLY-3 RATE (b)    |     1/13.69      1/14.38      0/15.00      1/13.85     |1/12.19      1/12.21      1/12.88      3/12.18      | 
|POLY-3 PERCENT (g) |     7.3%         7.0%         0.0%         7.2%        |8.2%         8.2%         7.8%         24.6%        | 
|TERMINAL (d)       |     1/13 (8%)    1/14 (7%)    0/15 (0%)    1/13 (8%)   |1/11 (9%)    1/10 (10%)   1/12 (8%)    2/10 (20%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      ---          183 (T)     |184 (T)      184 (T)      184 (T)      162          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.622N     P=0.748N     P=0.471N     P=0.765     |P=0.143      P=0.744      P=0.746N     P=0.276      | 
|POLY 3             |     P=0.610N     P=0.750N     P=0.482N     P=0.759N    |P=0.155      P=0.762N     P=0.750N     P=0.293      | 
|POLY 1.5           |     P=0.612N     P=0.754N     P=0.489N     P=0.759N    |P=0.156      P=0.759N     P=0.752N     P=0.296      | 
|POLY 6             |     P=0.608N     P=0.747N     P=0.475N     P=0.759N    |P=0.155      P=0.759      P=0.749N     P=0.290      | 
|LOGISTIC REGRESSION|     P=0.622N     P=0.748N     (e)          P=0.765     |P=0.141      P=0.744      P=0.746N     P=0.281      | 
|COCH-ARM / FISHERS |     P=0.618N     P=0.759N     P=0.500N     P=0.759N    |P=0.154      P=0.759N     P=0.759N     P=0.299      | 
|ORDER RESTRICTED   |     P=0.523N     (e)          (e)          (e)         |P=0.168      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/15 (53%)   8/15 (53%)   5/15 (33%)   6/15 (40%)  |14/15 (93%)  11/15 (73%)  14/15 (93%)  11/15 (73%)  | 
|POLY-3 RATE (b)    |     8/14.46      8/15.00      5/15.00      6/13.85     |14/14.35     11/13.39     14/15.00     11/12.18     | 
|POLY-3 PERCENT (g) |     55.3%        53.3%        33.3%        43.3%       |97.6%        82.1%        93.3%        90.3%        | 
|TERMINAL (d)       |     7/13 (54%)   7/14 (50%)   5/15 (33%)   6/13 (46%)  |11/11 (100%) 9/10 (90%)   11/12 (92%)  10/10 (100%) | 
|FIRST INCIDENCE    |     113          133          183 (T)      183 (T)     |73           115          110          162          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.237N     P=0.559N     P=0.157N     P=0.360N    |P=0.322N     P=0.330N     P=0.479N     P=0.322N     | 
|POLY 3             |     P=0.262N     P=0.600N     P=0.205N     P=0.398N    |P=0.489N     P=0.205N     P=0.637N     P=0.519N     | 
|POLY 1.5           |     P=0.251N     P=0.616N     P=0.216N     P=0.384N    |P=0.369N     P=0.184N     P=0.699N     P=0.311N     | 
|POLY 6             |     P=0.272N     P=0.581N     P=0.192N     P=0.411N    |P=0.611N     P=0.229N     P=0.560N     P=0.948N     | 
|LOGISTIC REGRESSION|     P=0.228N     P=0.610      P=0.268N     P=0.351N    |P=0.183N     P=0.127N     P=0.751N     P=0.103N     | 
|COCH-ARM / FISHERS |     P=0.228N     P=0.642N     P=0.231N     P=0.358N    |P=0.206N     P=0.165N     P=0.759N     P=0.165N     | 
|ORDER RESTRICTED   |     P=0.295N     (e)          (e)          (e)         |P=0.296N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    1/15 (7%)    2/15 (13%)  |3/15 (20%)   2/15 (13%)   4/15 (27%)   2/15 (13%)   | 
|POLY-3 RATE (b)    |     1/13.69      1/14.38      1/15.00      2/14.61     |3/12.19      2/12.21      4/15.00      2/11.87      | 
|POLY-3 PERCENT (g) |     7.3%         7.0%         6.7%         13.7%       |24.6%        16.4%        26.7%        16.9%        | 
|TERMINAL (d)       |     1/13 (8%)    1/14 (7%)    1/15 (7%)    1/13 (8%)   |3/11 (27%)   2/10 (20%)   1/12 (8%)    2/10 (20%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      114         |184 (T)      184 (T)      110          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.348      P=0.748N     P=0.732N     P=0.508     |P=0.494N     P=0.547N     P=0.551      P=0.547N     | 
|POLY 3             |     P=0.369      P=0.750N     P=0.740N     P=0.523     |P=0.480N     P=0.499N     P=0.620      P=0.513N     | 
|POLY 1.5           |     P=0.363      P=0.754N     P=0.748N     P=0.515     |P=0.479N     P=0.494N     P=0.583      P=0.505N     | 
|POLY 6             |     P=0.373      P=0.747N     P=0.733N     P=0.528     |P=0.485N     P=0.509N     P=0.649      P=0.527N     | 
|LOGISTIC REGRESSION|     P=0.342      P=0.748N     P=0.732N     P=0.481     |P=0.477N     P=0.547N     P=0.451      P=0.547N     | 
|COCH-ARM / FISHERS |     P=0.347      P=0.759N     P=0.759N     P=0.500     |P=0.478N     P=0.500N     P=0.500      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.427      (e)          (e)          (e)         |P=0.520N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/15 (27%)   2/15 (13%)   5/15 (33%)   4/15 (27%)  |3/15 (20%)   7/15 (47%)   5/15 (33%)   5/15 (33%)   | 
|POLY-3 RATE (b)    |     4/13.69      2/14.38      5/15.00      4/14.61     |3/12.85      7/12.21      5/12.88      5/12.18      | 
|POLY-3 PERCENT (g) |     29.2%        13.9%        33.3%        27.4%       |23.4%        57.3%        38.8%        41.0%        | 
|TERMINAL (d)       |     4/13 (31%)   2/14 (14%)   5/15 (33%)   3/13 (23%)  |2/11 (18%)   7/10 (70%)   5/12 (42%)   4/10 (40%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      114         |129          184 (T)      184 (T)      162          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.437      P=0.289N     P=0.601      P=0.650N    |P=0.386      P=0.085      P=0.389      P=0.307      | 
|POLY 3             |     P=0.476      P=0.301N     P=0.564      P=0.618N    |P=0.378      P=0.084      P=0.338      P=0.303      | 
|POLY 1.5           |     P=0.464      P=0.310N     P=0.540      P=0.631N    |P=0.400      P=0.100      P=0.347      P=0.320      | 
|POLY 6             |     P=0.483      P=0.294N     P=0.585      P=0.609N    |P=0.353      P=0.068      P=0.327      P=0.285      | 
|LOGISTIC REGRESSION|     P=0.440      P=0.289N     P=0.601      P=0.658     |P=0.398      P=0.114      P=0.365      P=0.329      | 
|COCH-ARM / FISHERS |     P=0.440      P=0.326N     P=0.500      P=0.659N    |P=0.427      P=0.123      P=0.341      P=0.341      | 
|ORDER RESTRICTED   |     P=0.469      (e)          (e)          (e)         |P=0.196      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/15 (7%)    0/14 (0%)    0/15 (0%)    2/15 (13%)   | 
|POLY-3 RATE (b)    |                                                        |1/12.19      0/11.64      0/12.88      2/11.87      | 
|POLY-3 PERCENT (g) |                                                        |8.2%         0.0%         0.0%         16.9%        | 
|TERMINAL (d)       |                                                        |1/11 (9%)    0/10 (0%)    0/12 (0%)    2/10 (20%)   | 
|FIRST INCIDENCE    |                                                        |184 (T)      ---          ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.227      P=0.519N     P=0.483N     P=0.465      | 
|POLY 3             |                                                        |P=0.242      P=0.509N     P=0.489N     P=0.490      | 
|POLY 1.5           |                                                        |P=0.244      P=0.509N     P=0.491N     P=0.496      | 
|POLY 6             |                                                        |P=0.239      P=0.510N     P=0.488N     P=0.480      | 
|LOGISTIC REGRESSION|                                                        |P=0.227      (e)          (e)          P=0.465      | 
|COCH-ARM / FISHERS |                                                        |P=0.248      P=0.517N     P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |                                                        |P=0.115      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |4/15 (27%)   1/15 (7%)    1/15 (7%)    2/15 (13%)   | 
|POLY-3 RATE (b)    |     0/13.69      0/14.38      0/15.00      0/13.85     |4/12.19      1/12.21      1/12.88      2/12.38      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |32.8%        8.2%         7.8%         16.2%        | 
|TERMINAL (d)       |     0/13 (0%)    0/14 (0%)    0/15 (0%)    0/13 (0%)   |4/11 (36%)   1/10 (10%)   1/12 (8%)    1/10 (10%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |184 (T)      184 (T)      184 (T)      145          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.320N     P=0.189N     P=0.136N     P=0.367N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.294N     P=0.154N     P=0.139N     P=0.314N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.298N     P=0.153N     P=0.144N     P=0.317N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.289N     P=0.159N     P=0.137N     P=0.314N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.310N     P=0.189N     P=0.136N     P=0.334N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.304N     P=0.165N     P=0.165N     P=0.326N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.104N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    2/15 (13%)   1/15 (7%)    1/15 (7%)   |2/15 (13%)   1/15 (7%)    1/15 (7%)    4/15 (27%)   | 
|POLY-3 RATE (b)    |     1/13.69      2/14.38      1/15.00      1/14.24     |2/12.19      1/12.21      1/12.88      4/12.18      | 
|POLY-3 PERCENT (g) |     7.3%         13.9%        6.7%         7.0%        |16.4%        8.2%         7.8%         32.8%        | 
|TERMINAL (d)       |     1/13 (8%)    2/14 (14%)   1/15 (7%)    0/13 (0%)   |2/11 (18%)   1/10 (10%)   1/12 (8%)    3/10 (30%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      155         |184 (T)      184 (T)      184 (T)      162          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.529N     P=0.527      P=0.732N     P=0.752N    |P=0.138      P=0.535N     P=0.468N     P=0.290      | 
|POLY 3             |     P=0.516N     P=0.517      P=0.740N     P=0.752N    |P=0.149      P=0.499N     P=0.480N     P=0.320      | 
|POLY 1.5           |     P=0.522N     P=0.511      P=0.748N     P=0.756N    |P=0.150      P=0.496N     P=0.484N     P=0.324      | 
|POLY 6             |     P=0.510N     P=0.523      P=0.733N     P=0.748N    |P=0.149      P=0.507N     P=0.479N     P=0.316      | 
|LOGISTIC REGRESSION|     P=0.532N     P=0.527      P=0.732N     P=0.765     |P=0.135      P=0.535N     P=0.468N     P=0.297      | 
|COCH-ARM / FISHERS |     P=0.531N     P=0.500      P=0.759N     P=0.759N    |P=0.152      P=0.500N     P=0.500N     P=0.326      | 
|ORDER RESTRICTED   |     P=0.572N     (e)          (e)          (e)         |P=0.106      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/15 (20%)   1/15 (7%)    2/15 (13%)   1/15 (7%)   |                                                    | 
|POLY-3 RATE (b)    |     3/13.69      1/14.38      2/15.00      1/13.85     |                                                    | 
|POLY-3 PERCENT (g) |     21.9%        7.0%         13.3%        7.2%        |                                                    | 
|TERMINAL (d)       |     3/13 (23%)   1/14 (7%)    2/15 (13%)   1/13 (8%)   |                                                    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.269N     P=0.271N     P=0.431N     P=0.297N    |                                                    | 
|POLY 3             |     P=0.275N     P=0.279N     P=0.457N     P=0.292N    |                                                    | 
|POLY 1.5           |     P=0.275N     P=0.285N     P=0.473N     P=0.294N    |                                                    | 
|POLY 6             |     P=0.276N     P=0.273N     P=0.442N     P=0.292N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.269N     P=0.271N     P=0.431N     P=0.297N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.270N     P=0.299N     P=0.500N     P=0.299N    |                                                    | 
|ORDER RESTRICTED   |     P=0.200N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    0/15 (0%)    2/15 (13%)  |0/15 (0%)    3/15 (20%)   1/15 (7%)    0/14 (0%)    | 
|POLY-3 RATE (b)    |     1/14.24      1/14.38      0/15.00      2/15.00     |0/12.19      3/13.40      1/13.50      0/11.42      | 
|POLY-3 PERCENT (g) |     7.0%         7.0%         0.0%         13.3%       |0.0%         22.4%        7.4%         0.0%         | 
|TERMINAL (d)       |     0/13 (0%)    1/14 (7%)    0/15 (0%)    0/13 (0%)   |0/11 (0%)    0/10 (0%)    0/12 (0%)    0/10 (0%)    | 
|FIRST INCIDENCE    |     141          183 (T)      ---          114         |---          126          133          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.374      P=0.752N     P=0.486N     P=0.516     |P=0.377N     P=0.124      P=0.516      (e)          | 
|POLY 3             |     P=0.378      P=0.758N     P=0.490N     P=0.519     |P=0.363N     P=0.122      P=0.520      (e)          | 
|POLY 1.5           |     P=0.374      P=0.759N     P=0.493N     P=0.512     |P=0.367N     P=0.116      P=0.515      (e)          | 
|POLY 6             |     P=0.382      P=0.759N     P=0.487N     P=0.523     |P=0.362N     P=0.127      P=0.525      (e)          | 
|LOGISTIC REGRESSION|     P=0.320      P=0.719      P=0.858N     P=0.425     |P=0.386N     P=0.101      P=0.421      (e)          | 
|COCH-ARM / FISHERS |     P=0.363      P=0.759N     P=0.500N     P=0.500     |P=0.382N     P=0.112      P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.283      (e)          (e)          (e)         |P=0.237N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    0/15 (0%)    2/15 (13%)   0/15 (0%)   |2/15 (13%)   1/15 (7%)    1/15 (7%)    1/15 (7%)    | 
|POLY-3 RATE (b)    |     1/13.69      0/14.38      2/15.00      0/13.85     |2/12.19      1/12.21      1/12.88      1/11.87      | 
|POLY-3 PERCENT (g) |     7.3%         0.0%         13.3%        0.0%        |16.4%        8.2%         7.8%         8.4%         | 
|TERMINAL (d)       |     1/13 (8%)    0/14 (0%)    2/15 (13%)   0/13 (0%)   |2/11 (18%)   1/10 (10%)   1/12 (8%)    1/10 (10%)   | 
|FIRST INCIDENCE    |     183 (T)      ---          183 (T)      ---         |184 (T)      184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.462N     P=0.485N     P=0.551      P=0.500N    |P=0.422N     P=0.535N     P=0.468N     P=0.535N     | 
|POLY 3             |     P=0.465N     P=0.490N     P=0.532      P=0.498N    |P=0.410N     P=0.499N     P=0.480N     P=0.510N     | 
|POLY 1.5           |     P=0.463N     P=0.494N     P=0.520      P=0.498N    |P=0.409N     P=0.496N     P=0.484N     P=0.504N     | 
|POLY 6             |     P=0.468N     P=0.487N     P=0.543      P=0.498N    |P=0.412N     P=0.507N     P=0.479N     P=0.520N     | 
|LOGISTIC REGRESSION|     P=0.462N     (e)          P=0.551      (e)         |P=0.422N     P=0.535N     P=0.468N     P=0.535N     | 
|COCH-ARM / FISHERS |     P=0.460N     P=0.500N     P=0.500      P=0.500N    |P=0.406N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.317N     (e)          (e)          (e)         |P=0.407N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 06                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |2/15 (13%)   0/15 (0%)    1/15 (7%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |                                                        |2/12.19      0/12.21      1/12.88      0/11.87      | 
|POLY-3 PERCENT (g) |                                                        |16.4%        0.0%         7.8%         0.0%         | 
|TERMINAL (d)       |                                                        |2/11 (18%)   0/10 (0%)    1/12 (8%)    0/10 (0%)    | 
|FIRST INCIDENCE    |                                                        |184 (T)      ---          184 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.189N     P=0.256N     P=0.468N     P=0.256N     | 
|POLY 3             |                                                        |P=0.183N     P=0.229N     P=0.480N     P=0.235N     | 
|POLY 1.5           |                                                        |P=0.184N     P=0.227N     P=0.484N     P=0.232N     | 
|POLY 6             |                                                        |P=0.183N     P=0.233N     P=0.479N     P=0.241N     | 
|LOGISTIC REGRESSION|                                                        |P=0.189N     (e)          P=0.468N     (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.184N     P=0.241N     P=0.500N     P=0.241N     | 
|ORDER RESTRICTED   |                                                        |P=0.072N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |7/15 (47%)   6/15 (40%)   10/15 (67%)  6/15 (40%)   | 
|POLY-3 RATE (b)    |                                                        |7/12.19      6/12.64      10/12.88     6/12.68      | 
|POLY-3 PERCENT (g) |                                                        |57.4%        47.5%        77.7%        47.3%        | 
|TERMINAL (d)       |                                                        |7/11 (64%)   5/10 (50%)   10/12 (83%)  5/10 (50%)   | 
|FIRST INCIDENCE    |                                                        |184 (T)      153          184 (T)      105          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.574      P=0.589N     P=0.279      P=0.584N     | 
|POLY 3             |                                                        |P=0.477N     P=0.463N     P=0.247      P=0.459N     | 
|POLY 1.5           |                                                        |P=0.485N     P=0.469N     P=0.249      P=0.467N     | 
|POLY 6             |                                                        |P=0.493N     P=0.459N     P=0.244      P=0.469N     | 
|LOGISTIC REGRESSION|                                                        |P=0.552N     P=0.515N     P=0.279      P=0.524N     | 
|COCH-ARM / FISHERS |                                                        |P=0.517N     P=0.500N     P=0.231      P=0.500N     | 
|ORDER RESTRICTED   |                                                        |P=0.381N     (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).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.