https://ntp.niehs.nih.gov/go/20449

TDMS Study 97013-05 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: 05                                                                                     TIME: 08:37:58       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-65406                              ROUTE: DOSED WATER                                             NTP C#: 97013E       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
------------------------------------------------------------------------------------------------------------------------------------
                                                            FINAL#1 MICE                                                            
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE 001    0 MG/L                                                                        
                                       INCLUDE 002    0 MG/L                                                                        
                                       INCLUDE 003    175 MG/L                                                                      
                                       INCLUDE 004    175 MG/L                                                                      
                                       INCLUDE 005    350 MG/L                                                                      
                                       INCLUDE 006    350 MG/L                                                                      
                                       INCLUDE 007    700 MG/L                                                                      
                                       INCLUDE 008    700 MG/L                                                                      
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 06/11/04       
EXPERIMENT: 97013 TEST: 05                                                                                     TIME: 08:37:58       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-65406                              ROUTE: DOSED WATER                                             NTP C#: 97013E       
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                                 Mineralization                                                                               
                                       Nephropathy                                                                                  
Kidney: Renal Tubule                   Degeneration                                                                                 
                                       Dilatation                                                                                   
                                       Hypertrophy                                                                                  
Spleen                                 Hematopoietic Cell Proliferation                                                             
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Kidney                                 Nephropathy                                                                                  
Liver: Hepatocyte                      Fatty Change                                                                                 
                                       Hypertrophy                                                                                  
                                       Vacuolization Cytoplasmic                                                                    
===============================================================                                                                     
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/15 (40%)   7/15 (47%)   7/15 (47%)   9/15 (60%)  |0/15 (0%)    0/15 (0%)    1/15 (7%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     6/14.64      7/12.65      7/14.13      9/15.00     |0/10.97      0/13.15      1/13.04      0/14.39      | 
|POLY-3 PERCENT (g) |     41.0%        55.3%        49.5%        60.0%       |0.0%         0.0%         7.7%         0.0%         | 
|TERMINAL (d)       |     5/13 (39%)   7/12 (58%)   6/12 (50%)   8/14 (57%)  |0/10 (0%)    0/13 (0%)    0/11 (0%)    0/13 (0%)    | 
|FIRST INCIDENCE    |     129          183 (T)      164          154         |---          ---          164          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.272      P=0.420      P=0.445      P=0.310     |P=0.729      (e)          P=0.552      (e)          | 
|POLY 3             |     P=0.227      P=0.360      P=0.466      P=0.255     |P=0.773N     (e)          P=0.534      (e)          | 
|POLY 1.5           |     P=0.212      P=0.399      P=0.480      P=0.246     |P=0.757      (e)          P=0.524      (e)          | 
|POLY 6             |     P=0.244      P=0.341      P=0.450      P=0.268     |P=0.772N     (e)          P=0.540      (e)          | 
|LOGISTIC REGRESSION|     P=0.225      P=0.414      P=0.500      P=0.191     |P=0.693      (e)          P=0.504      (e)          | 
|COCH-ARM / FISHERS |     P=0.180      P=0.500      P=0.500      P=0.233     |P=0.695      (e)          P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.233      (e)          (e)          (e)         |P=0.414      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    1/15 (7%)    1/15 (7%)    1/15 (7%)   |8/15 (53%)   8/15 (53%)   7/15 (47%)   10/15 (67%)  | 
|POLY-3 RATE (b)    |     0/13.99      1/12.65      1/13.85      1/14.60     |8/12.72      8/13.15      7/13.71      10/14.68     | 
|POLY-3 PERCENT (g) |     0.0%         7.9%         7.2%         6.9%        |62.9%        60.8%        51.0%        68.1%        | 
|TERMINAL (d)       |     0/13 (0%)    1/12 (8%)    1/12 (8%)    1/14 (7%)   |6/10 (60%)   8/13 (62%)   5/11 (46%)   9/13 (69%)   | 
|FIRST INCIDENCE    |     ---          183 (T)      183 (T)      183 (T)     |64           184 (T)      126          164          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.410      P=0.484      P=0.484      P=0.515     |P=0.510      P=0.378N     P=0.396N     P=0.605N     | 
|POLY 3             |     P=0.406      P=0.480      P=0.498      P=0.508     |P=0.447      P=0.615N     P=0.413N     P=0.546      | 
|POLY 1.5           |     P=0.398      P=0.484      P=0.499      P=0.505     |P=0.404      P=0.631N     P=0.449N     P=0.495      | 
|POLY 6             |     P=0.413      P=0.479      P=0.495      P=0.512     |P=0.463      P=0.585N     P=0.390N     P=0.576      | 
|LOGISTIC REGRESSION|     (e)          P=0.484      P=0.484      P=0.515     |P=0.426      P=0.551N     P=0.463N     P=0.466      | 
|COCH-ARM / FISHERS |     P=0.382      P=0.500      P=0.500      P=0.500     |P=0.284      P=0.642N     P=0.500N     P=0.355      | 
|ORDER RESTRICTED   |     P=0.311      (e)          (e)          (e)         |P=0.470      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Casts Protein                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    2/15 (13%)   1/15 (7%)    1/15 (7%)   |0/15 (0%)    1/15 (7%)    3/15 (20%)   2/15 (13%)   | 
|POLY-3 RATE (b)    |     1/13.99      2/12.65      1/13.85      1/14.60     |0/10.97      1/13.15      3/12.74      2/14.39      | 
|POLY-3 PERCENT (g) |     7.2%         15.8%        7.2%         6.9%        |0.0%         7.6%         23.5%        13.9%        | 
|TERMINAL (d)       |     1/13 (8%)    2/12 (17%)   1/12 (8%)    1/14 (7%)   |0/10 (0%)    1/13 (8%)    3/11 (27%)   2/13 (15%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |---          184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.498N     P=0.471      P=0.747      P=0.748N    |P=0.200      P=0.552      P=0.129      P=0.295      | 
|POLY 3             |     P=0.515N     P=0.464      P=0.759      P=0.751N    |P=0.250      P=0.536      P=0.132      P=0.298      | 
|POLY 1.5           |     P=0.520N     P=0.472      P=0.760      P=0.755N    |P=0.226      P=0.525      P=0.124      P=0.280      | 
|POLY 6             |     P=0.510N     P=0.463      P=0.756      P=0.748N    |P=0.257      P=0.546      P=0.133      P=0.306      | 
|LOGISTIC REGRESSION|     P=0.498N     P=0.471      P=0.747      P=0.748N    |(e)          P=0.552      P=0.129      P=0.295      | 
|COCH-ARM / FISHERS |     P=0.531N     P=0.500      P=0.759N     P=0.759N    |P=0.154      P=0.500      P=0.112      P=0.241      | 
|ORDER RESTRICTED   |     P=0.536N     (e)          (e)          (e)         |P=0.127      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    2/15 (13%)   3/15 (20%)   0/15 (0%)   |2/15 (13%)   3/15 (20%)   1/15 (7%)    2/15 (13%)   | 
|POLY-3 RATE (b)    |     0/13.99      2/12.65      3/13.85      0/14.60     |2/10.97      3/13.15      1/12.74      2/14.39      | 
|POLY-3 PERCENT (g) |     0.0%         15.8%        21.7%        0.0%        |18.2%        22.8%        7.9%         13.9%        | 
|TERMINAL (d)       |     0/13 (0%)    2/12 (17%)   3/12 (25%)   0/14 (0%)   |2/10 (20%)   3/13 (23%)   1/11 (9%)    2/13 (15%)   | 
|FIRST INCIDENCE    |     ---          183 (T)      183 (T)      ---         |184 (T)      184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.498N     P=0.217      P=0.100      (e)         |P=0.417N     P=0.627      P=0.465N     P=0.602N     | 
|POLY 3             |     P=0.504N     P=0.207      P=0.103      (e)         |P=0.411N     P=0.587      P=0.446N     P=0.595N     | 
|POLY 1.5           |     P=0.514N     P=0.213      P=0.104      (e)         |P=0.432N     P=0.560      P=0.461N     P=0.622N     | 
|POLY 6             |     P=0.494N     P=0.207      P=0.099      (e)         |P=0.405N     P=0.610      P=0.443N     P=0.583N     | 
|LOGISTIC REGRESSION|     (e)          P=0.217      P=0.100      (e)         |P=0.417N     P=0.627      P=0.465N     P=0.602N     | 
|COCH-ARM / FISHERS |     P=0.531N     P=0.241      P=0.112      (e)         |P=0.500N     P=0.500      P=0.500N     P=0.701N     | 
|ORDER RESTRICTED   |     P=0.179N     (e)          (e)          (e)         |P=0.415N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    2/15 (13%)  |0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     0/13.99      0/12.65      0/13.85      2/15.00     |0/10.97      0/13.15      0/12.74      0/14.39      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         13.3%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/13 (0%)    0/12 (0%)    0/12 (0%)    1/14 (7%)   |0/10 (0%)    0/13 (0%)    0/11 (0%)    0/13 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          154         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.058      (e)          (e)          P=0.256     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.047 *    (e)          (e)          P=0.248     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.045 *    (e)          (e)          P=0.241     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.049 *    (e)          (e)          P=0.256     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.032 *    (e)          (e)          P=0.148     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.044 *    (e)          (e)          P=0.241     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.031 *    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/15 (27%)   3/15 (20%)   4/15 (27%)   11/15 (73%) |1/15 (7%)    0/15 (0%)    1/15 (7%)    4/15 (27%)   | 
|POLY-3 RATE (b)    |     4/14.35      3/13.47      4/13.85      11/14.60    |1/10.97      0/13.15      1/12.74      4/14.39      | 
|POLY-3 PERCENT (g) |     27.9%        22.3%        28.9%        75.4%       |9.1%         0.0%         7.9%         27.8%        | 
|TERMINAL (d)       |     3/13 (23%)   2/12 (17%)   4/12 (33%)   11/14 (79%) |1/10 (10%)   0/13 (0%)    1/11 (9%)    4/13 (31%)   | 
|FIRST INCIDENCE    |     158          103          183 (T)      183 (T)     |184 (T)      ---          184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.006 **   P=0.550N     P=0.613      P=0.026 *   |P=0.043 *    P=0.448N     P=0.744N     P=0.251      | 
|POLY 3             |     P<0.001 **   P=0.537N     P=0.636      P=0.008 **  |P=0.035 *    P=0.464N     P=0.728N     P=0.257      | 
|POLY 1.5           |     P<0.001 **   P=0.529N     P=0.646      P=0.008 **  |P=0.033 *    P=0.475N     P=0.738N     P=0.231      | 
|POLY 6             |     P<0.001 **   P=0.541N     P=0.617      P=0.007 **  |P=0.034 *    P=0.454N     P=0.726N     P=0.269      | 
|LOGISTIC REGRESSION|     P=0.003 **   P=0.457N     P=0.655      P=0.018 *   |P=0.043 *    (e)          P=0.744N     P=0.251      | 
|COCH-ARM / FISHERS |     P=0.002 **   P=0.500N     P=0.659N     P=0.013 *   |P=0.029 *    P=0.500N     P=0.759N     P=0.165      | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.047 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    4/15 (27%)   4/15 (27%)   9/15 (60%)  |0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     0/13.99      4/12.65      4/14.13      9/15.00     |0/10.97      0/13.15      0/12.74      0/14.39      | 
|POLY-3 PERCENT (g) |     0.0%         31.6%        28.3%        60.0%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/13 (0%)    4/12 (33%)   3/12 (25%)   8/14 (57%)  |0/10 (0%)    0/13 (0%)    0/11 (0%)    0/13 (0%)    | 
|FIRST INCIDENCE    |     ---          183 (T)      164          154         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.045 *    P=0.056      P=0.002 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   P=0.032 *    P=0.045 *    P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   P=0.035 *    P=0.045 *    P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   P=0.032 *    P=0.045 *    P<0.001 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.045 *    P=0.053      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.050      P=0.050      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/15 (27%)   11/15 (73%)  14/15 (93%)  15/15 (100%)|0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     4/13.99      11/13.24     14/14.41     15/15.00    |0/10.97      0/13.15      0/12.74      0/14.39      | 
|POLY-3 PERCENT (g) |     28.6%        83.1%        97.2%        100.0%      |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     4/13 (31%)   10/12 (83%)  12/12 (100%) 14/14 (100%)|0/10 (0%)    0/13 (0%)    0/11 (0%)    0/13 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      136          164          154         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.008 **   P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.005 **   P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.013 *    P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    3/15 (20%)   6/15 (40%)   11/15 (73%) |1/15 (7%)    2/15 (13%)   5/15 (33%)   2/15 (13%)   | 
|POLY-3 RATE (b)    |     1/13.99      3/12.65      6/14.13      11/15.00    |1/10.97      2/13.15      5/12.74      2/14.39      | 
|POLY-3 PERCENT (g) |     7.2%         23.7%        42.5%        73.3%       |9.1%         15.2%        39.2%        13.9%        | 
|TERMINAL (d)       |     1/13 (8%)    3/12 (25%)   5/12 (42%)   10/14 (71%) |1/10 (10%)   2/13 (15%)   5/11 (46%)   2/13 (15%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      164          154         |184 (T)      184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.267      P=0.040 *    P<0.001 **  |P=0.454      P=0.594      P=0.100      P=0.594      | 
|POLY 3             |     P<0.001 **   P=0.259      P=0.034 *    P<0.001 **  |P=0.538      P=0.564      P=0.109      P=0.595      | 
|POLY 1.5           |     P<0.001 **   P=0.268      P=0.034 *    P<0.001 **  |P=0.497      P=0.544      P=0.099      P=0.571      | 
|POLY 6             |     P<0.001 **   P=0.258      P=0.033 *    P<0.001 **  |P=0.548      P=0.582      P=0.110      P=0.605      | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.267      P=0.039 *    P<0.001 **  |P=0.454      P=0.594      P=0.100      P=0.594      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.299      P=0.040 *    P<0.001 **  |P=0.363      P=0.500      P=0.084      P=0.500      | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.239      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    0/15 (0%)    0/15 (0%)   |1/15 (7%)    1/15 (7%)    3/15 (20%)   1/15 (7%)    | 
|POLY-3 RATE (b)    |     1/13.99      1/13.47      0/13.85      0/14.60     |1/10.97      1/13.15      3/13.04      1/14.39      | 
|POLY-3 PERCENT (g) |     7.2%         7.4%         0.0%         0.0%        |9.1%         7.6%         23.0%        7.0%         | 
|TERMINAL (d)       |     1/13 (8%)    0/12 (0%)    0/12 (0%)    0/14 (0%)   |1/10 (10%)   1/13 (8%)    2/11 (18%)   1/13 (8%)    | 
|FIRST INCIDENCE    |     183 (T)      103          ---          ---         |184 (T)      184 (T)      164          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.231N     P=0.744      P=0.516N     P=0.485N    |P=0.595N     P=0.705N     P=0.352      P=0.705N     | 
|POLY 3             |     P=0.234N     P=0.753      P=0.502N     P=0.492N    |P=0.571N     P=0.720N     P=0.362      P=0.697N     | 
|POLY 1.5           |     P=0.235N     P=0.753      P=0.501N     P=0.495N    |P=0.593N     P=0.734N     P=0.341      P=0.714N     | 
|POLY 6             |     P=0.234N     P=0.755      P=0.505N     P=0.488N    |P=0.567N     P=0.708N     P=0.373      P=0.690N     | 
|LOGISTIC REGRESSION|     P=0.291N     P=0.660N     (e)          (e)         |P=0.590N     P=0.705N     P=0.347      P=0.705N     | 
|COCH-ARM / FISHERS |     P=0.233N     P=0.759N     P=0.500N     P=0.500N    |P=0.558      P=0.759N     P=0.299      P=0.759N     | 
|ORDER RESTRICTED   |     P=0.236N     (e)          (e)          (e)         |P=0.494N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/15 (47%)   6/15 (40%)   7/15 (47%)   5/15 (33%)  |11/15 (73%)  11/15 (73%)  13/15 (87%)  14/15 (93%)  | 
|POLY-3 RATE (b)    |     7/15.00      6/13.47      7/15.00      5/14.60     |11/11.75     11/13.15     13/13.33     14/14.68     | 
|POLY-3 PERCENT (g) |     46.7%        44.5%        46.7%        34.3%       |93.6%        83.6%        97.5%        95.4%        | 
|TERMINAL (d)       |     5/13 (39%)   5/12 (42%)   4/12 (33%)   5/14 (36%)  |10/10 (100%) 11/13 (85%)  11/11 (100%) 13/13 (100%) | 
|FIRST INCIDENCE    |     129          103          136          183 (T)     |110          184 (T)      164          164          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.266N     P=0.576N     P=0.590      P=0.319N    |P=0.376      P=0.147N     P=0.579      P=0.697N     | 
|POLY 3             |     P=0.309N     P=0.600N     P=0.638      P=0.380N    |P=0.382      P=0.437N     P=0.785      P=0.806      | 
|POLY 1.5           |     P=0.307N     P=0.572N     P=0.638      P=0.370N    |P=0.246      P=0.528N     P=0.517      P=0.540      | 
|POLY 6             |     P=0.318N     P=0.621N     P=0.638      P=0.394N    |P=0.442      P=0.340N     P=0.998      P=0.950N     | 
|LOGISTIC REGRESSION|     P=0.349N     P=0.475N     (e)          P=0.413N    |P=0.629      P=0.315N     P=0.782N     P=0.655N     | 
|COCH-ARM / FISHERS |     P=0.313N     P=0.500N     P=0.642N     P=0.355N    |P=0.079      P=0.659N     P=0.326      P=0.165      | 
|ORDER RESTRICTED   |     P=0.398N     (e)          (e)          (e)         |P=0.297      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/15 (20%)   1/15 (7%)    3/15 (20%)   3/15 (20%)  |0/15 (0%)    2/15 (13%)   0/15 (0%)    1/15 (7%)    | 
|POLY-3 RATE (b)    |     3/13.99      1/12.65      3/13.85      3/14.60     |0/10.97      2/13.15      0/12.74      1/14.39      | 
|POLY-3 PERCENT (g) |     21.4%        7.9%         21.7%        20.6%       |0.0%         15.2%        0.0%         7.0%         | 
|TERMINAL (d)       |     3/13 (23%)   1/12 (8%)    3/12 (25%)   3/14 (21%)  |0/10 (0%)    2/13 (15%)   0/11 (0%)    1/13 (8%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |---          184 (T)      ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.504      P=0.327N     P=0.636      P=0.638N    |P=0.587      P=0.295      (e)          P=0.552      | 
|POLY 3             |     P=0.504      P=0.335N     P=0.668      P=0.651N    |P=0.644      P=0.274      (e)          P=0.553      | 
|POLY 1.5           |     P=0.489      P=0.327N     P=0.670      P=0.659N    |P=0.618      P=0.260      (e)          P=0.540      | 
|POLY 6             |     P=0.514      P=0.336N     P=0.662      P=0.643N    |P=0.656      P=0.287      (e)          P=0.559      | 
|LOGISTIC REGRESSION|     P=0.504      P=0.327N     P=0.636      P=0.638N    |(e)          P=0.295      (e)          P=0.552      | 
|COCH-ARM / FISHERS |     P=0.453      P=0.299N     P=0.674N     P=0.674N    |P=0.540      P=0.241      (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.530      (e)          (e)          (e)         |P=0.351      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Fatty Change                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |0/15 (0%)    4/15 (27%)   8/15 (53%)   10/15 (67%)  | 
|POLY-3 RATE (b)    |     0/13.99      0/12.65      0/13.85      0/14.60     |0/10.97      4/13.15      8/13.42      10/14.39     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         30.4%        59.6%        69.5%        | 
|TERMINAL (d)       |     0/13 (0%)    0/12 (0%)    0/12 (0%)    0/14 (0%)   |0/10 (0%)    4/13 (31%)   7/11 (64%)   10/13 (77%)  | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          184 (T)      126          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.089      P=0.003 **   P<0.001 **   | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.067      P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.059      P<0.001 **   P<0.001 **   | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.076      P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.089      P=0.003 **   P<0.001 **   | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.050      P<0.001 **   P<0.001 **   | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |1/15 (7%)    2/15 (13%)   8/15 (53%)   12/15 (80%)  | 
|POLY-3 RATE (b)    |     0/13.99      0/12.65      0/13.85      0/14.60     |1/10.97      2/13.15      8/13.42      12/14.68     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |9.1%         15.2%        59.6%        81.7%        | 
|TERMINAL (d)       |     0/13 (0%)    0/12 (0%)    0/12 (0%)    0/14 (0%)   |1/10 (10%)   2/13 (15%)   7/11 (64%)   11/13 (85%)  | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |184 (T)      184 (T)      126          164          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.594      P=0.013 *    P<0.001 **   | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.564      P=0.009 **   P<0.001 **   | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.544      P=0.006 **   P<0.001 **   | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.582      P=0.010 *    P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.594      P=0.012 *    P<0.001 **   | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P<0.001 **   P=0.500      P=0.007 **   P<0.001 **   | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/15 (40%)   4/15 (27%)   3/15 (20%)   3/15 (20%)  |2/15 (13%)   5/15 (33%)   4/15 (27%)   8/15 (53%)   | 
|POLY-3 RATE (b)    |     6/13.99      4/12.65      3/13.85      3/14.60     |2/10.97      5/13.15      4/13.04      8/14.39      | 
|POLY-3 PERCENT (g) |     42.9%        31.6%        21.7%        20.6%       |18.2%        38.0%        30.7%        55.6%        | 
|TERMINAL (d)       |     6/13 (46%)   4/12 (33%)   3/12 (25%)   3/14 (21%)  |2/10 (20%)   5/13 (39%)   3/11 (27%)   8/13 (62%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      184 (T)      164          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.125N     P=0.405N     P=0.251N     P=0.175N    |P=0.046 *    P=0.314      P=0.389      P=0.063      | 
|POLY 3             |     P=0.132N     P=0.423N     P=0.214N     P=0.189N    |P=0.054      P=0.273      P=0.412      P=0.062      | 
|POLY 1.5           |     P=0.142N     P=0.406N     P=0.213N     P=0.199N    |P=0.043 *    P=0.244      P=0.384      P=0.047 *    | 
|POLY 6             |     P=0.125N     P=0.424N     P=0.220N     P=0.179N    |P=0.057      P=0.299      P=0.426      P=0.069      | 
|LOGISTIC REGRESSION|     P=0.125N     P=0.405N     P=0.251N     P=0.175N    |P=0.054      P=0.314      P=0.400      P=0.063      | 
|COCH-ARM / FISHERS |     P=0.162N     P=0.350N     P=0.213N     P=0.213N    |P=0.022 *    P=0.195      P=0.326      P=0.025 *    | 
|ORDER RESTRICTED   |     P=0.143N     (e)          (e)          (e)         |P=0.039 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    2/15 (13%)   0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     1/13.99      2/12.65      0/13.85      0/14.60     |0/10.97      0/13.15      0/12.74      0/14.39      | 
|POLY-3 PERCENT (g) |     7.2%         15.8%        0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/13 (8%)    2/12 (17%)   0/12 (0%)    0/14 (0%)   |0/10 (0%)    0/13 (0%)    0/11 (0%)    0/13 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.175N     P=0.471      P=0.516N     P=0.485N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.182N     P=0.464      P=0.502N     P=0.492N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.183N     P=0.472      P=0.501N     P=0.495N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.180N     P=0.463      P=0.505N     P=0.488N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.175N     P=0.471      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.184N     P=0.500      P=0.500N     P=0.500N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.136N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |0/15 (0%)    2/15 (13%)   1/15 (7%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |                                                        |0/10.97      2/13.15      1/12.74      0/14.39      | 
|POLY-3 PERCENT (g) |                                                        |0.0%         15.2%        7.9%         0.0%         | 
|TERMINAL (d)       |                                                        |0/10 (0%)    2/13 (15%)   1/11 (9%)    0/13 (0%)    | 
|FIRST INCIDENCE    |                                                        |---          184 (T)      184 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.413N     P=0.295      P=0.519      (e)          | 
|POLY 3             |                                                        |P=0.356N     P=0.274      P=0.530      (e)          | 
|POLY 1.5           |                                                        |P=0.382N     P=0.260      P=0.521      (e)          | 
|POLY 6             |                                                        |P=0.344N     P=0.287      P=0.532      (e)          | 
|LOGISTIC REGRESSION|                                                        |(e)          P=0.295      P=0.519      (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.460N     P=0.241      P=0.500      (e)          | 
|ORDER RESTRICTED   |                                                        |P=0.308N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/3 (67%)    0/0 (0%)     0/0 (0%)     1/1 (100%)  |                                                    | 
|POLY-3 RATE (b)    |     2/3.00       0/0.00       0/0.00       1/1.00      |                                                    | 
|POLY-3 PERCENT (g) |     66.7%        0.0%         0.0%         100.0%      |                                                    | 
|TERMINAL (d)       |     2/3 (67%)    0/0 (0%)     0/0 (0%)     1/1 (100%)  |                                                    | 
|FIRST INCIDENCE    |     183 (T)      ---          ---          183 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.500      P=1.000      P=1.000N     P=0.718     |                                                    | 
|POLY 3             |     (e)          (e)          (e)          P=0.691     |                                                    | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.691     |                                                    | 
|POLY 6             |     (e)          (e)          (e)          P=0.691     |                                                    | 
|LOGISTIC REGRESSION|     P=0.500      (e)          (e)          P=0.718     |                                                    | 
|COCH-ARM / FISHERS |     P=0.500      P=1.000      P=1.000      P=0.750     |                                                    | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            Page 10      
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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland: Duct                                                                                                            | 
|     Ectasia                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/3 (100%)   0/0 (0%)     0/0 (0%)     1/1 (100%)  |                                                    | 
|POLY-3 RATE (b)    |     3/3.00       0/0.00       0/0.00       1/1.00      |                                                    | 
|POLY-3 PERCENT (g) |     100.0%       0.0%         0.0%         100.0%      |                                                    | 
|TERMINAL (d)       |     3/3 (100%)   0/0 (0%)     0/0 (0%)     1/1 (100%)  |                                                    | 
|FIRST INCIDENCE    |     183 (T)      ---          ---          183 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |                                                    | 
|POLY 3             |     (e)          (e)          (e)          (e)         |                                                    | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |                                                    | 
|POLY 6             |     (e)          (e)          (e)          (e)         |                                                    | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |                                                    | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |                                                    | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/15 (27%)   2/15 (13%)   0/15 (0%)    0/15 (0%)   |2/15 (13%)   3/15 (20%)   3/15 (20%)   1/15 (7%)    | 
|POLY-3 RATE (b)    |     4/15.00      2/13.47      0/13.85      0/14.60     |2/10.97      3/13.15      3/13.04      1/14.39      | 
|POLY-3 PERCENT (g) |     26.7%        14.9%        0.0%         0.0%        |18.2%        22.8%        23.0%        7.0%         | 
|TERMINAL (d)       |     2/13 (15%)   1/12 (8%)    0/12 (0%)    0/14 (0%)   |2/10 (20%)   3/13 (23%)   2/11 (18%)   1/13 (8%)    | 
|FIRST INCIDENCE    |     129          103          ---          ---         |184 (T)      184 (T)      164          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.017N*    P=0.385N     P=0.070N     P=0.060N    |P=0.257N     P=0.627      P=0.561      P=0.406N     | 
|POLY 3             |     P=0.011N*    P=0.381N     P=0.055N     P=0.048N*   |P=0.225N     P=0.587      P=0.583      P=0.404N     | 
|POLY 1.5           |     P=0.011N*    P=0.365N     P=0.050N     P=0.047N*   |P=0.249N     P=0.560      P=0.558      P=0.428N     | 
|POLY 6             |     P=0.012N*    P=0.392N     P=0.062N     P=0.050N    |P=0.219N     P=0.610      P=0.596      P=0.394N     | 
|LOGISTIC REGRESSION|     P=0.018N*    P=0.191N     P=0.040N*    P=0.075N    |P=0.237N     P=0.627      P=0.575      P=0.406N     | 
|COCH-ARM / FISHERS |     P=0.015N*    P=0.326N     P=0.050N     P=0.050N    |P=0.334N     P=0.500      P=0.500      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.008N**   (e)          (e)          (e)         |P=0.284N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            Page 11      
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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/15 (20%)   2/15 (13%)   3/15 (20%)   3/15 (20%)  |                                                    | 
|POLY-3 RATE (b)    |     3/14.64      2/13.47      3/13.85      3/14.60     |                                                    | 
|POLY-3 PERCENT (g) |     20.5%        14.9%        21.7%        20.6%       |                                                    | 
|TERMINAL (d)       |     2/13 (15%)   1/12 (8%)    3/12 (25%)   3/14 (21%)  |                                                    | 
|FIRST INCIDENCE    |     129          103          183 (T)      183 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.566      P=0.541N     P=0.638      P=0.639N    |                                                    | 
|POLY 3             |     P=0.536      P=0.540N     P=0.645      P=0.670     |                                                    | 
|POLY 1.5           |     P=0.533      P=0.530N     P=0.656      P=0.670     |                                                    | 
|POLY 6             |     P=0.536      P=0.543N     P=0.629      P=0.670     |                                                    | 
|LOGISTIC REGRESSION|     P=0.476      P=0.362N     P=0.676N     P=0.609     |                                                    | 
|COCH-ARM / FISHERS |     P=0.522      P=0.500N     P=0.674N     P=0.674N    |                                                    | 
|ORDER RESTRICTED   |     P=0.639      (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    1/14 (7%)    1/15 (7%)    1/15 (7%)   |2/14 (14%)   1/15 (7%)    1/15 (7%)    1/14 (7%)    | 
|POLY-3 RATE (b)    |     0/13.99      1/13.18      1/14.44      1/15.00     |2/12.24      1/13.15      1/13.74      1/14.00      | 
|POLY-3 PERCENT (g) |     0.0%         7.6%         6.9%         6.7%        |16.3%        7.6%         7.3%         7.1%         | 
|TERMINAL (d)       |     0/13 (0%)    0/12 (0%)    0/12 (0%)    0/14 (0%)   |0/10 (0%)    1/13 (8%)    0/11 (0%)    0/13 (0%)    | 
|FIRST INCIDENCE    |     ---          72           136          154         |64           184 (T)      34           162          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.407      P=0.500      P=0.514      P=0.514     |P=0.364N     P=0.462N     P=0.491N     P=0.429N     | 
|POLY 3             |     P=0.419      P=0.488      P=0.506      P=0.514     |P=0.381N     P=0.474N     P=0.459N     P=0.452N     | 
|POLY 1.5           |     P=0.408      P=0.486      P=0.504      P=0.508     |P=0.388N     P=0.474N     P=0.457N     P=0.463N     | 
|POLY 6             |     P=0.432      P=0.492      P=0.507      P=0.520     |P=0.379N     P=0.472N     P=0.470N     P=0.447N     | 
|LOGISTIC REGRESSION|     P=0.078      (e)          P=0.391      P=0.301     |P=0.513      P=0.608N     P=0.792N     P=0.595      | 
|COCH-ARM / FISHERS |     P=0.388      P=0.483      P=0.500      P=0.500     |P=0.410N     P=0.473N     P=0.473N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.320      (e)          (e)          (e)         |P=0.348N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 05                                            Page 12      
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/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/15 (13%)   1/15 (7%)    0/15 (0%)    1/15 (7%)   |1/15 (7%)    1/14 (7%)    2/15 (13%)   1/15 (7%)    | 
|POLY-3 RATE (b)    |     2/13.99      1/12.65      0/13.85      1/14.60     |1/10.97      1/13.08      2/12.74      1/14.68      | 
|POLY-3 PERCENT (g) |     14.3%        7.9%         0.0%         6.9%        |9.1%         7.7%         15.7%        6.8%         | 
|TERMINAL (d)       |     2/13 (15%)   1/12 (8%)    0/12 (0%)    1/14 (7%)   |1/10 (10%)   1/13 (8%)    2/11 (18%)   0/13 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      ---          183 (T)     |184 (T)      184 (T)      184 (T)      164          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.340N     P=0.529N     P=0.253N     P=0.473N    |P=0.585N     P=0.705N     P=0.535      P=0.692N     | 
|POLY 3             |     P=0.352N     P=0.536N     P=0.233N     P=0.485N    |P=0.568N     P=0.721N     P=0.554      P=0.692N     | 
|POLY 1.5           |     P=0.355N     P=0.528N     P=0.232N     P=0.491N    |P=0.586N     P=0.738N     P=0.538      P=0.711N     | 
|POLY 6             |     P=0.350N     P=0.537N     P=0.236N     P=0.479N    |P=0.561N     P=0.707N     P=0.557      P=0.680N     | 
|LOGISTIC REGRESSION|     P=0.340N     P=0.529N     (e)          P=0.473N    |P=0.585N     P=0.705N     P=0.535      P=0.748N     | 
|COCH-ARM / FISHERS |     P=0.363N     P=0.500N     P=0.241N     P=0.500N    |P=0.601      P=0.741      P=0.500      P=0.759N     | 
|ORDER RESTRICTED   |     P=0.208N     (e)          (e)          (e)         |P=0.581N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |9/15 (60%)   8/15 (53%)   9/15 (60%)   8/15 (53%)   | 
|POLY-3 RATE (b)    |                                                        |9/10.97      8/13.15      9/12.74      8/14.68      | 
|POLY-3 PERCENT (g) |                                                        |82.1%        60.8%        70.6%        54.5%        | 
|TERMINAL (d)       |                                                        |9/10 (90%)   8/13 (62%)   9/11 (82%)   7/13 (54%)   | 
|FIRST INCIDENCE    |                                                        |184 (T)      184 (T)      184 (T)      164          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.210N     P=0.149N     P=0.535N     P=0.178N     | 
|POLY 3             |                                                        |P=0.161N     P=0.240N     P=0.429N     P=0.145N     | 
|POLY 1.5           |                                                        |P=0.227N     P=0.323N     P=0.506N     P=0.229N     | 
|POLY 6             |                                                        |P=0.132N     P=0.179N     P=0.404N     P=0.103N     | 
|LOGISTIC REGRESSION|                                                        |P=0.155N     P=0.149N     P=0.535N     P=0.122N     | 
|COCH-ARM / FISHERS |                                                        |P=0.465N     P=0.500N     P=0.645N     P=0.500N     | 
|ORDER RESTRICTED   |                                                        |P=0.111N     (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).