National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/20725

TDMS Study 97013-09 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                          WATER DISINFECTION MODEL (SODIUM BROMATE)                      DATE: 06/18/04       
EXPERIMENT: 97013 TEST: 09                                                                                     TIME: 11:08:17       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: DOSED WATER                                             NTP C#: 97013A       
PATHOLOGIST: TOFT, JOHN                                                                                        CAS: 7789-38-0       
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                           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    80 MG/L                                                                       
                                       INCLUDE 004    80 MG/L                                                                       
                                       INCLUDE 005    400 MG/L                                                                      
                                       INCLUDE 006    400 MG/L                                                                      
                                       INCLUDE 007    800 MG/L                                                                      
                                       INCLUDE 008    800 MG/L                                                                      
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                          WATER DISINFECTION MODEL (SODIUM BROMATE)                      DATE: 06/18/04       
EXPERIMENT: 97013 TEST: 09                                                                                     TIME: 11:08:17       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: DOSED WATER                                             NTP C#: 97013A       
PATHOLOGIST: TOFT, JOHN                                                                                        CAS: 7789-38-0       
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF        WATER DISINFECTION MODEL (SODIUM BR                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Kidney                                 Nephropathy                                                                                  
Kidney: Renal Tubule                   Degeneration                                                                                 
                                       Hypertrophy                                                                                  
Pituitary Gland: Pars Distalis         Cyst                                                                                         
Spleen                                 Hematopoietic Cell Proliferation                                                             
Thymus                                 Cyst                                                                                         
Thyroid Gland: Follicle                Depletion Secretory                                                                          
Thyroid Gland: Follicular Cell         Hypertrophy                                                                                  
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Kidney                                 Nephropathy                                                                                  
Kidney: Artery                         Inflammation Chronic                                                                         
Kidney: Renal Tubule                   Degeneration                                                                                 
                                       Hypertrophy                                                                                  
Liver: Hepatocyte                      Vacuolization Cytoplasmic                                                                    
Lymph Node, Mandibular                 Hyperplasia Lymphoid                                                                         
Pituitary Gland: Pars Distalis         Hypertrophy                                                                                  
Skin: Epidermis                        Hyperkeratosis                                                                               
                                       Hyperplasia Focal                                                                            
Thyroid Gland                          Infiltration Cellular Lymphocyte                                                             
Thyroid Gland: Follicle                Depletion Secretory                                                                          
Thyroid Gland: Follicular Cell         Hypertrophy                                                                                  
===============================================================                                                                     
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SO
DIUM BR                                                                                                                             
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/15 (27%)   6/15 (40%)   6/15 (40%)   4/15 (27%)  |0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     4/13.82      6/14.58      6/14.49      4/14.62     |0/12.01      0/10.24      0/12.33      0/12.46      | 
|POLY-3 PERCENT (g) |     28.9%        41.2%        41.4%        27.4%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     4/13 (31%)   6/13 (46%)   6/14 (43%)   4/14 (29%)  |0/10 (0%)    0/9 (0%)     0/10 (0%)    0/12 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.386N     P=0.346      P=0.403      P=0.615N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.423N     P=0.389      P=0.384      P=0.623N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.423N     P=0.391      P=0.388      P=0.622N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.425N     P=0.384      P=0.379      P=0.626N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.386N     P=0.346      P=0.403      P=0.615N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.458N     P=0.350      P=0.350      P=0.659N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.464N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    0/15 (0%)    1/15 (7%)   |4/15 (27%)   6/15 (40%)   2/15 (13%)   2/15 (13%)   | 
|POLY-3 RATE (b)    |     1/13.82      1/14.58      0/14.49      1/14.62     |4/12.21      6/10.76      2/12.33      2/13.00      | 
|POLY-3 PERCENT (g) |     7.2%         6.9%         0.0%         6.8%        |32.8%        55.8%        16.2%        15.4%        | 
|TERMINAL (d)       |     1/13 (8%)    1/13 (8%)    0/14 (0%)    1/14 (7%)   |3/10 (30%)   5/9 (56%)    2/10 (20%)   1/12 (8%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      ---          183 (T)     |171          144          184 (T)      142          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.566N     P=0.765      P=0.485N     P=0.748N    |P=0.051N     P=0.264      P=0.334N     P=0.273N     | 
|POLY 3             |     P=0.583N     P=0.749N     P=0.491N     P=0.748N    |P=0.057N     P=0.246      P=0.317N     P=0.292N     | 
|POLY 1.5           |     P=0.583N     P=0.748N     P=0.490N     P=0.748N    |P=0.066N     P=0.281      P=0.312N     P=0.309N     | 
|POLY 6             |     P=0.584N     P=0.750N     P=0.492N     P=0.749N    |P=0.052N     P=0.229      P=0.328N     P=0.279N     | 
|LOGISTIC REGRESSION|     P=0.566N     P=0.765      (e)          P=0.748N    |P=0.062N     P=0.225      P=0.311N     P=0.316N     | 
|COCH-ARM / FISHERS |     P=0.589N     P=0.759N     P=0.500N     P=0.759N    |P=0.087N     P=0.350      P=0.326N     P=0.326N     | 
|ORDER RESTRICTED   |     P=0.518N     (e)          (e)          (e)         |P=0.078N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis                                                                                                                       | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    2/15 (13%)   2/15 (13%)  |                                                    | 
|POLY-3 RATE (b)    |     0/13.82      0/14.58      2/14.49      2/14.62     |                                                    | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         13.8%        13.7%       |                                                    | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    2/14 (14%)   2/14 (14%)  |                                                    | 
|FIRST INCIDENCE    |     ---          ---          183 (T)      183 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.076      (e)          P=0.252      P=0.252     |                                                    | 
|POLY 3             |     P=0.070      (e)          P=0.242      P=0.244     |                                                    | 
|POLY 1.5           |     P=0.070      (e)          P=0.243      P=0.245     |                                                    | 
|POLY 6             |     P=0.069      (e)          P=0.240      P=0.243     |                                                    | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.252      P=0.252     |                                                    | 
|COCH-ARM / FISHERS |     P=0.065      (e)          P=0.241      P=0.241     |                                                    | 
|ORDER RESTRICTED   |     P=0.115      (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    7/15 (47%)   10/15 (67%)  14/15 (93%) |2/15 (13%)   2/15 (13%)   10/15 (67%)  13/15 (87%)  | 
|POLY-3 RATE (b)    |     1/13.82      7/14.58      10/14.49     14/14.62    |2/12.01      2/10.24      10/12.33     13/13.00     | 
|POLY-3 PERCENT (g) |     7.2%         48.0%        69.0%        95.8%       |16.7%        19.5%        81.1%        100.0%       | 
|TERMINAL (d)       |     1/13 (8%)    7/13 (54%)   10/14 (71%)  14/14 (100%)|2/10 (20%)   2/9 (22%)    10/10 (100%) 12/12 (100%) | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      184 (T)      184 (T)      142          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.019 *    P=0.002 **   P<0.001 **  |P<0.001 **   P=0.667      P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P=0.016 *    P<0.001 **   P<0.001 **  |P<0.001 **   P=0.642      P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.016 *    P<0.001 **   P<0.001 **  |P<0.001 **   P=0.665      P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.015 *    P<0.001 **   P<0.001 **  |P<0.001 **   P=0.628      P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.019 *    P=0.002 **   P<0.001 **  |P<0.001 **   P=0.667      P<0.001 **   P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.018 *    P<0.001 **   P<0.001 **  |P<0.001 **   P=0.701N     P=0.004 **   P<0.001 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Artery                                                                                                                   | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |2/15 (13%)   0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     0/13.82      0/14.58      0/14.49      0/14.62     |2/12.21      0/10.24      0/12.33      0/12.46      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |16.4%        0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    0/14 (0%)    0/14 (0%)   |1/10 (10%)   0/9 (0%)     0/10 (0%)    0/12 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |171          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.145N     P=0.284N     P=0.249N     P=0.220N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.125N     P=0.272N     P=0.227N     P=0.225N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.134N     P=0.255N     P=0.225N     P=0.229N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.120N     P=0.285N     P=0.232N     P=0.223N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.146N     P=0.263N     P=0.226N     P=0.226N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.158N     P=0.241N     P=0.241N     P=0.241N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.024N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    10/15 (67%) |0/15 (0%)    0/15 (0%)    2/15 (13%)   8/15 (53%)   | 
|POLY-3 RATE (b)    |     0/13.82      0/14.58      0/14.49      10/14.62    |0/12.01      0/10.24      2/12.33      8/12.46      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         68.4%       |0.0%         0.0%         16.2%        64.2%        | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    0/14 (0%)    10/14 (71%) |0/10 (0%)    0/9 (0%)     2/10 (20%)   8/12 (67%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          183 (T)     |---          ---          184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.234      P=0.003 **   | 
|POLY 3             |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.235      P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.237      P<0.001 **   | 
|POLY 6             |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.232      P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P<0.001 **  |(e)          (e)          P=0.234      P=0.003 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.241      P<0.001 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    1/15 (7%)    0/15 (0%)   |1/15 (7%)    2/15 (13%)   0/15 (0%)    1/15 (7%)    | 
|POLY-3 RATE (b)    |     0/13.82      0/14.58      1/14.49      0/14.62     |1/12.01      2/10.24      0/12.33      1/12.46      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         6.9%         0.0%        |8.3%         19.5%        0.0%         8.0%         | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    1/14 (7%)    0/14 (0%)   |1/10 (10%)   2/9 (22%)    0/10 (0%)    1/12 (8%)    | 
|FIRST INCIDENCE    |     ---          ---          183 (T)      ---         |184 (T)      184 (T)      ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.660      (e)          P=0.515      (e)         |P=0.352N     P=0.461      P=0.500N     P=0.724N     | 
|POLY 3             |     P=0.662      (e)          P=0.509      (e)         |P=0.417N     P=0.442      P=0.495N     P=0.754N     | 
|POLY 1.5           |     P=0.662      (e)          P=0.510      (e)         |P=0.418N     P=0.464      P=0.494N     P=0.759N     | 
|POLY 6             |     P=0.661      (e)          P=0.508      (e)         |P=0.417N     P=0.429      P=0.497N     P=0.750N     | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.515      (e)         |P=0.352N     P=0.461      (e)          P=0.724N     | 
|COCH-ARM / FISHERS |     P=0.650      (e)          P=0.500      (e)         |P=0.422N     P=0.500      P=0.500N     P=0.759N     | 
|ORDER RESTRICTED   |     P=0.389      (e)          (e)          (e)         |P=0.315N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    2/15 (13%)  |0/15 (0%)    1/15 (7%)    5/15 (33%)   12/15 (80%)  | 
|POLY-3 RATE (b)    |     0/13.82      0/14.58      0/14.49      2/14.62     |0/12.01      1/10.24      5/12.33      12/12.46     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         13.7%       |0.0%         9.8%         40.6%        96.3%        | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    0/14 (0%)    2/14 (14%)  |0/10 (0%)    1/9 (11%)    5/10 (50%)   12/12 (100%) | 
|FIRST INCIDENCE    |     ---          ---          ---          183 (T)     |---          184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.047 *    (e)          (e)          P=0.252     |P<0.001 **   P=0.479      P=0.022 *    P<0.001 **   | 
|POLY 3             |     P=0.040 *    (e)          (e)          P=0.244     |P<0.001 **   P=0.468      P=0.016 *    P<0.001 **   | 
|POLY 1.5           |     P=0.040 *    (e)          (e)          P=0.245     |P<0.001 **   P=0.480      P=0.017 *    P<0.001 **   | 
|POLY 6             |     P=0.039 *    (e)          (e)          P=0.243     |P<0.001 **   P=0.461      P=0.014 *    P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.252     |(e)          P=0.479      P=0.022 *    P<0.001 **   | 
|COCH-ARM / FISHERS |     P=0.041 *    (e)          (e)          P=0.241     |P<0.001 **   P=0.500      P=0.021 *    P<0.001 **   | 
|ORDER RESTRICTED   |     P=0.030 *    (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/15 (60%)   4/15 (27%)   10/15 (67%)  7/15 (47%)  |11/15 (73%)  9/15 (60%)   10/15 (67%)  12/15 (80%)  | 
|POLY-3 RATE (b)    |     9/15.00      4/14.58      10/15.00     7/14.62     |11/12.21     9/10.24      10/12.33     12/12.46     | 
|POLY-3 PERCENT (g) |     60.0%        27.4%        66.7%        47.9%       |90.1%        87.9%        81.1%        96.3%        | 
|TERMINAL (d)       |     7/13 (54%)   4/13 (31%)   9/14 (64%)   7/14 (50%)  |10/10 (100%) 9/9 (100%)   10/10 (100%) 12/12 (100%) | 
|FIRST INCIDENCE    |     29           183 (T)      144          183 (T)     |171          184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.551      P=0.086N     P=0.580      P=0.306N    |P=0.338N     P=0.557N     P=0.517N     P=0.500N     | 
|POLY 3             |     P=0.449      P=0.074N     P=0.500      P=0.387N    |P=0.398      P=0.737N     P=0.475N     P=0.588      | 
|POLY 1.5           |     P=0.454      P=0.070N     P=0.500      P=0.375N    |P=0.301      P=0.520N     P=0.449N     P=0.517      | 
|POLY 6             |     P=0.442      P=0.080N     P=0.500      P=0.405N    |P=0.479      P=0.798      P=0.549N     P=0.647      | 
|LOGISTIC REGRESSION|     P=0.422      P=0.090N     (e)          P=0.405N    |P=0.707N     P=0.833      P=0.549N     P=0.808      | 
|COCH-ARM / FISHERS |     P=0.461      P=0.070N     P=0.500      P=0.358N    |P=0.272      P=0.350N     P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.363      (e)          (e)          (e)         |P=0.259      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/15 (40%)   4/15 (27%)   7/15 (47%)   4/15 (27%)  |5/15 (33%)   0/15 (0%)    5/15 (33%)   5/15 (33%)   | 
|POLY-3 RATE (b)    |     6/13.82      4/14.58      7/14.49      4/14.62     |5/12.01      0/10.24      5/12.33      5/12.46      | 
|POLY-3 PERCENT (g) |     43.4%        27.4%        48.3%        27.4%       |41.6%        0.0%         40.6%        40.1%        | 
|TERMINAL (d)       |     6/13 (46%)   4/13 (31%)   7/14 (50%)   4/14 (29%)  |5/10 (50%)   0/9 (0%)     5/10 (50%)   5/12 (42%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      ---          184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.357N     P=0.346N     P=0.572      P=0.296N    |P=0.290      P=0.029N*    P=0.669      P=0.515N     | 
|POLY 3             |     P=0.404N     P=0.312N     P=0.545      P=0.311N    |P=0.247      P=0.025N*    P=0.638N     P=0.628N     | 
|POLY 1.5           |     P=0.405N     P=0.312N     P=0.548      P=0.311N    |P=0.206      P=0.020N*    P=0.632N     P=0.645N     | 
|POLY 6             |     P=0.405N     P=0.316N     P=0.539      P=0.313N    |P=0.278      P=0.027N*    P=0.648N     P=0.614N     | 
|LOGISTIC REGRESSION|     P=0.357N     P=0.346N     P=0.572      P=0.296N    |P=0.290      (e)          P=0.669      P=0.515N     | 
|COCH-ARM / FISHERS |     P=0.432N     P=0.350N     P=0.500      P=0.350N    |P=0.172      P=0.021N*    P=0.650N     P=0.650N     | 
|ORDER RESTRICTED   |     P=0.302N     (e)          (e)          (e)         |P=0.254      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    1/15 (7%)    0/15 (0%)   |0/15 (0%)    3/15 (20%)   0/15 (0%)    1/15 (7%)    | 
|POLY-3 RATE (b)    |     0/13.82      0/14.58      1/14.49      0/14.62     |0/12.01      3/10.24      0/12.33      1/13.46      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         6.9%         0.0%        |0.0%         29.3%        0.0%         7.4%         | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    1/14 (7%)    0/14 (0%)   |0/10 (0%)    3/9 (33%)    0/10 (0%)    0/12 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          183 (T)      ---         |---          184 (T)      ---          9            | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.660      (e)          P=0.515      (e)         |P=0.420N     P=0.093      (e)          P=0.500      | 
|POLY 3             |     P=0.662      (e)          P=0.509      (e)         |P=0.483N     P=0.074      (e)          P=0.523      | 
|POLY 1.5           |     P=0.662      (e)          P=0.510      (e)         |P=0.474N     P=0.084      (e)          P=0.518      | 
|POLY 6             |     P=0.661      (e)          P=0.508      (e)         |P=0.488N     P=0.068      (e)          P=0.527      | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.515      (e)         |P=0.480N     P=0.093      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.650      (e)          P=0.500      (e)         |P=0.474N     P=0.112      (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.389      (e)          (e)          (e)         |P=0.223      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/15 (20%)   1/15 (7%)    3/15 (20%)   1/15 (7%)   |0/15 (0%)    4/15 (27%)   2/15 (13%)   5/15 (33%)   | 
|POLY-3 RATE (b)    |     3/14.00      1/14.58      3/15.00      1/14.62     |0/12.01      4/10.24      2/12.66      5/12.46      | 
|POLY-3 PERCENT (g) |     21.4%        6.9%         20.0%        6.8%        |0.0%         39.1%        15.8%        40.1%        | 
|TERMINAL (d)       |     2/13 (15%)   1/13 (8%)    2/14 (14%)   1/14 (7%)   |0/10 (0%)    4/9 (44%)    1/10 (10%)   5/12 (42%)   | 
|FIRST INCIDENCE    |     171          183 (T)      144          183 (T)     |---          184 (T)      161          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.343N     P=0.303N     P=0.636N     P=0.283N    |P=0.128      P=0.039 *    P=0.240      P=0.038 *    | 
|POLY 3             |     P=0.360N     P=0.283N     P=0.637N     P=0.282N    |P=0.065      P=0.024 *    P=0.242      P=0.017 *    | 
|POLY 1.5           |     P=0.360N     P=0.280N     P=0.639N     P=0.279N    |P=0.062      P=0.030 *    P=0.240      P=0.016 *    | 
|POLY 6             |     P=0.361N     P=0.289N     P=0.637N     P=0.287N    |P=0.068      P=0.021 *    P=0.243      P=0.018 *    | 
|LOGISTIC REGRESSION|     P=0.380N     P=0.281N     P=0.669      P=0.280N    |P=0.096      P=0.039 *    P=0.236      P=0.038 *    | 
|COCH-ARM / FISHERS |     P=0.368N     P=0.299N     P=0.674N     P=0.299N    |P=0.069      P=0.050      P=0.241      P=0.021 *    | 
|ORDER RESTRICTED   |     P=0.210N     (e)          (e)          (e)         |P=0.009 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Parathyroid Gland                                                                                                                | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/1 (100%)   0/0 (0%)     2/2 (100%)   0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|POLY-3 RATE (b)    |     1/1.00       0/0.00       2/2.00       0/0.00      |0/0.00       0/0.00       0/0.00       0/0.00       | 
|POLY-3 PERCENT (g) |     100.0%       0.0%         100.0%       0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/1 (100%)   0/0 (0%)     2/2 (100%)   0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     183 (T)      ---          183 (T)      ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/14 (0%)    4/15 (27%)   0/15 (0%)   |1/15 (7%)    0/15 (0%)    0/15 (0%)    2/15 (13%)   | 
|POLY-3 RATE (b)    |     0/13.82      0/13.98      4/15.00      0/14.62     |1/12.01      0/10.24      0/12.33      2/13.00      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         26.7%        0.0%        |8.3%         0.0%         0.0%         15.4%        | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    3/14 (21%)   0/14 (0%)   |1/10 (10%)   0/9 (0%)     0/10 (0%)    1/12 (8%)    | 
|FIRST INCIDENCE    |     ---          ---          144          ---         |184 (T)      ---          ---          142          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.449      (e)          P=0.071      (e)         |P=0.258      P=0.521N     P=0.500N     P=0.552      | 
|POLY 3             |     P=0.440      (e)          P=0.056      (e)         |P=0.242      P=0.532N     P=0.495N     P=0.528      | 
|POLY 1.5           |     P=0.445      (e)          P=0.054      (e)         |P=0.226      P=0.520N     P=0.494N     P=0.514      | 
|POLY 6             |     P=0.430      (e)          P=0.057      (e)         |P=0.255      P=0.539N     P=0.497N     P=0.543      | 
|LOGISTIC REGRESSION|     P=0.405      (e)          P=0.047 *    (e)         |P=0.212      (e)          (e)          P=0.502      | 
|COCH-ARM / FISHERS |     P=0.433      (e)          P=0.050      (e)         |P=0.204      P=0.500N     P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.096      (e)          (e)          (e)         |P=0.147      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/14 (0%)    0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    0/15 (0%)    6/15 (40%)   | 
|POLY-3 RATE (b)    |     0/13.82      0/13.98      0/14.49      0/14.62     |0/12.01      0/10.24      0/12.33      6/12.46      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         48.1%        | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    0/14 (0%)    0/14 (0%)   |0/10 (0%)    0/9 (0%)     0/10 (0%)    6/12 (50%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P<0.001 **   (e)          (e)          P=0.018 *    | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P<0.001 **   (e)          (e)          P=0.005 **   | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P<0.001 **   (e)          (e)          P=0.004 **   | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P<0.001 **   (e)          (e)          P=0.005 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          P=0.018 *    | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P<0.001 **   (e)          (e)          P=0.008 **   | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin: Epidermis                                                                                                                  | 
|     Hyperkeratosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     0/2 (0%)     0/4 (0%)     1/3 (33%)   |0/6 (0%)     0/5 (0%)     0/2 (0%)     2/7 (29%)    | 
|POLY-3 RATE (b)    |     0/0.00       0/1.98       0/4.00       1/3.00      |0/5.89       0/4.48       0/0.80       2/7.00       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         33.3%       |0.0%         0.0%         0.0%         28.6%        | 
|TERMINAL (d)       |     0/0 (0%)     0/1 (0%)     0/4 (0%)     1/3 (33%)   |0/5 (0%)     0/4 (0%)     0/0 (0%)     2/7 (29%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          183 (T)     |---          ---          ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.357      (e)          (e)          P=1.000N    |P=0.102      (e)          (e)          P=0.308      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.072      (e)          (e)          P=0.261      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.069      (e)          (e)          P=0.259      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.077      (e)          (e)          P=0.266      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=1.000N    |(e)          (e)          (e)          P=0.308      | 
|COCH-ARM / FISHERS |     P=0.293      (e)          (e)          P=1.000     |P=0.065      (e)          (e)          P=0.269      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.033 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin: Epidermis                                                                                                                  | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     0/2 (0%)     1/4 (25%)    2/3 (67%)   |0/6 (0%)     0/5 (0%)     0/2 (0%)     2/7 (29%)    | 
|POLY-3 RATE (b)    |     0/0.00       0/1.98       1/4.00       2/3.00      |0/5.89       0/4.48       0/0.80       2/7.00       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         25.0%        66.7%       |0.0%         0.0%         0.0%         28.6%        | 
|TERMINAL (d)       |     0/0 (0%)     0/1 (0%)     1/4 (25%)    2/3 (67%)   |0/5 (0%)     0/4 (0%)     0/0 (0%)     2/7 (29%)    | 
|FIRST INCIDENCE    |     ---          ---          183 (T)      183 (T)     |---          ---          ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.227      (e)          P=1.000N     P=1.000N    |P=0.102      (e)          (e)          P=0.308      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.072      (e)          (e)          P=0.261      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.069      (e)          (e)          P=0.259      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.077      (e)          (e)          P=0.266      | 
|LOGISTIC REGRESSION|     (e)          (e)          P=1.000N     P=1.000N    |(e)          (e)          (e)          P=0.308      | 
|COCH-ARM / FISHERS |     P=0.138      (e)          P=1.000      P=1.000     |P=0.065      (e)          (e)          P=0.269      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.033 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    0/15 (0%)    1/15 (7%)   |1/15 (7%)    1/15 (7%)    1/15 (7%)    2/15 (13%)   | 
|POLY-3 RATE (b)    |     1/14.00      1/14.60      0/14.49      1/15.00     |1/13.01      1/10.80      1/13.32      2/14.46      | 
|POLY-3 PERCENT (g) |     7.1%         6.9%         0.0%         6.7%        |7.7%         9.3%         7.5%         13.8%        | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    0/14 (0%)    0/14 (0%)   |0/10 (0%)    0/9 (0%)     0/10 (0%)    0/12 (0%)    | 
|FIRST INCIDENCE    |     171          182          ---          156         |28           140          28           9            | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.577N     P=0.752N     P=0.500N     P=0.753N    |P=0.339      P=0.751      P=0.764      P=0.484      | 
|POLY 3             |     P=0.583N     P=0.751N     P=0.493N     P=0.745N    |P=0.410      P=0.719      P=0.756N     P=0.537      | 
|POLY 1.5           |     P=0.583N     P=0.750N     P=0.491N     P=0.746N    |P=0.396      P=0.729      P=0.755N     P=0.529      | 
|POLY 6             |     P=0.583N     P=0.755N     P=0.497N     P=0.745N    |P=0.420      P=0.716      P=0.759N     P=0.545      | 
|LOGISTIC REGRESSION|     P=0.630N     P=0.771N     P=0.512N     P=0.741     |P=0.354      P=0.767N     (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.589N     P=0.759N     P=0.500N     P=0.759N    |P=0.339      P=0.759N     P=0.759N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.517N     (e)          (e)          (e)         |P=0.463      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    0/15 (0%)    0/15 (0%)    3/15 (20%)  |2/15 (13%)   3/15 (20%)   1/15 (7%)    4/15 (27%)   | 
|POLY-3 RATE (b)    |     1/13.82      0/14.58      0/14.49      3/14.62     |2/12.01      3/12.20      1/12.33      4/12.46      | 
|POLY-3 PERCENT (g) |     7.2%         0.0%         0.0%         20.5%       |16.7%        24.6%        8.1%         32.1%        | 
|TERMINAL (d)       |     1/13 (8%)    0/13 (0%)    0/14 (0%)    3/14 (21%)  |2/10 (20%)   1/9 (11%)    1/10 (10%)   4/12 (33%)   | 
|FIRST INCIDENCE    |     183 (T)      ---          ---          183 (T)     |184 (T)      49           184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.076      P=0.500N     P=0.485N     P=0.325     |P=0.407      P=0.484      P=0.500N     P=0.415      | 
|POLY 3             |     P=0.061      P=0.489N     P=0.491N     P=0.319     |P=0.326      P=0.508      P=0.491N     P=0.340      | 
|POLY 1.5           |     P=0.062      P=0.489N     P=0.490N     P=0.319     |P=0.314      P=0.520      P=0.489N     P=0.329      | 
|POLY 6             |     P=0.061      P=0.491N     P=0.492N     P=0.317     |P=0.337      P=0.497      P=0.495N     P=0.351      | 
|LOGISTIC REGRESSION|     P=0.076      (e)          (e)          P=0.325     |P=0.314      P=0.540      P=0.500N     P=0.415      | 
|COCH-ARM / FISHERS |     P=0.065      P=0.500N     P=0.500N     P=0.299     |P=0.314      P=0.500      P=0.500N     P=0.326      | 
|ORDER RESTRICTED   |     P=0.036 *    (e)          (e)          (e)         |P=0.270      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperkeratosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    2/15 (13%)   0/15 (0%)   |4/15 (27%)   3/15 (20%)   3/15 (20%)   7/15 (47%)   | 
|POLY-3 RATE (b)    |     1/14.00      1/14.60      2/15.00      0/14.62     |4/13.01      3/10.80      3/13.32      7/15.00      | 
|POLY-3 PERCENT (g) |     7.1%         6.9%         13.3%        0.0%        |30.7%        27.8%        22.5%        46.7%        | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    1/14 (7%)    0/14 (0%)   |3/10 (30%)   2/9 (22%)    2/10 (20%)   4/12 (33%)   | 
|FIRST INCIDENCE    |     171          182          144          ---         |28           140          28           9            | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.363N     P=0.752N     P=0.516      P=0.500N    |P=0.189      P=0.550N     P=0.500N     P=0.320      | 
|POLY 3             |     P=0.363N     P=0.751N     P=0.524      P=0.491N    |P=0.192      P=0.612N     P=0.486N     P=0.322      | 
|POLY 1.5           |     P=0.362N     P=0.750N     P=0.523      P=0.490N    |P=0.165      P=0.586N     P=0.483N     P=0.294      | 
|POLY 6             |     P=0.366N     P=0.755N     P=0.524      P=0.495N    |P=0.215      P=0.620N     P=0.492N     P=0.350      | 
|LOGISTIC REGRESSION|     P=0.409N     P=0.771N     P=0.456      P=0.514N    |P=0.086      P=0.504N     P=0.530N     P=0.208      | 
|COCH-ARM / FISHERS |     P=0.371N     P=0.759N     P=0.500      P=0.500N    |P=0.101      P=0.500N     P=0.500N     P=0.225      | 
|ORDER RESTRICTED   |     P=0.273N     (e)          (e)          (e)         |P=0.199      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    1/15 (7%)    2/15 (13%)   2/15 (13%)  |5/15 (33%)   3/15 (20%)   3/15 (20%)   8/15 (53%)   | 
|POLY-3 RATE (b)    |     1/13.82      1/14.60      2/15.00      2/14.62     |5/13.12      3/10.80      3/13.32      8/15.00      | 
|POLY-3 PERCENT (g) |     7.2%         6.9%         13.3%        13.7%       |38.1%        27.8%        22.5%        53.3%        | 
|TERMINAL (d)       |     1/13 (8%)    0/13 (0%)    1/14 (7%)    2/14 (14%)  |3/10 (30%)   2/9 (22%)    2/10 (20%)   5/12 (42%)   | 
|FIRST INCIDENCE    |     183 (T)      182          144          183 (T)     |28           140          28           9            | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.343      P=0.752N     P=0.525      P=0.527     |P=0.177      P=0.410N     P=0.351N     P=0.347      | 
|POLY 3             |     P=0.331      P=0.749N     P=0.529      P=0.520     |P=0.168      P=0.462N     P=0.329N     P=0.337      | 
|POLY 1.5           |     P=0.331      P=0.748N     P=0.525      P=0.520     |P=0.142      P=0.431N     P=0.325N     P=0.308      | 
|POLY 6             |     P=0.330      P=0.750N     P=0.533      P=0.518     |P=0.188      P=0.476N     P=0.338N     P=0.364      | 
|LOGISTIC REGRESSION|     P=0.297      P=0.758N     P=0.474      P=0.527     |P=0.073      P=0.350N     P=0.359N     P=0.219      | 
|COCH-ARM / FISHERS |     P=0.311      P=0.759N     P=0.500      P=0.500     |P=0.085      P=0.341N     P=0.341N     P=0.231      | 
|ORDER RESTRICTED   |     P=0.455      (e)          (e)          (e)         |P=0.135      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    3/15 (20%)   0/15 (0%)   |                                                    | 
|POLY-3 RATE (b)    |     0/13.82      0/14.58      3/14.49      0/14.62     |                                                    | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         20.7%        0.0%        |                                                    | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    3/14 (21%)   0/14 (0%)   |                                                    | 
|FIRST INCIDENCE    |     ---          ---          183 (T)      ---         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.493      (e)          P=0.128      (e)         |                                                    | 
|POLY 3             |     P=0.491      (e)          P=0.114      (e)         |                                                    | 
|POLY 1.5           |     P=0.490      (e)          P=0.115      (e)         |                                                    | 
|POLY 6             |     P=0.490      (e)          P=0.113      (e)         |                                                    | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.128      (e)         |                                                    | 
|COCH-ARM / FISHERS |     P=0.470      (e)          P=0.112      (e)         |                                                    | 
|ORDER RESTRICTED   |     P=0.151      (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    0/15 (0%)    3/15 (20%)   2/15 (13%)  |                                                    | 
|POLY-3 RATE (b)    |     1/13.82      0/14.58      3/14.49      2/14.62     |                                                    | 
|POLY-3 PERCENT (g) |     7.2%         0.0%         20.7%        13.7%       |                                                    | 
|TERMINAL (d)       |     1/13 (8%)    0/13 (0%)    3/14 (21%)   2/14 (14%)  |                                                    | 
|FIRST INCIDENCE    |     183 (T)      ---          183 (T)      183 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.201      P=0.500N     P=0.325      P=0.527     |                                                    | 
|POLY 3             |     P=0.186      P=0.489N     P=0.315      P=0.520     |                                                    | 
|POLY 1.5           |     P=0.186      P=0.489N     P=0.317      P=0.520     |                                                    | 
|POLY 6             |     P=0.185      P=0.491N     P=0.313      P=0.518     |                                                    | 
|LOGISTIC REGRESSION|     P=0.201      (e)          P=0.325      P=0.527     |                                                    | 
|COCH-ARM / FISHERS |     P=0.176      P=0.500N     P=0.299      P=0.500     |                                                    | 
|ORDER RESTRICTED   |     P=0.184      (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/15 (13%)   1/15 (7%)    1/14 (7%)    2/15 (13%)  |3/15 (20%)   3/15 (20%)   3/15 (20%)   4/15 (27%)   | 
|POLY-3 RATE (b)    |     2/14.00      1/14.60      1/13.49      2/15.00     |3/13.02      3/12.16      3/14.53      4/15.00      | 
|POLY-3 PERCENT (g) |     14.3%        6.9%         7.4%         13.3%       |23.0%        24.7%        20.7%        26.7%        | 
|TERMINAL (d)       |     1/13 (8%)    0/13 (0%)    1/13 (8%)    1/14 (7%)   |0/10 (0%)    0/9 (0%)     0/10 (0%)    1/12 (8%)    | 
|FIRST INCIDENCE    |     171          182          183 (T)      156         |123          100          28           9            | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.542      P=0.491N     P=0.500N     P=0.674N    |P=0.450      P=0.581      P=0.658      P=0.521      | 
|POLY 3             |     P=0.534      P=0.485N     P=0.513N     P=0.673N    |P=0.509      P=0.640      P=0.618N     P=0.582      | 
|POLY 1.5           |     P=0.531      P=0.483N     P=0.509N     P=0.675N    |P=0.494      P=0.653      P=0.617N     P=0.575      | 
|POLY 6             |     P=0.538      P=0.491N     P=0.520N     P=0.673N    |P=0.512      P=0.635      P=0.628N     P=0.583      | 
|LOGISTIC REGRESSION|     P=0.504      P=0.491N     P=0.515N     P=0.693     |P=0.325      P=0.656N     P=0.645      P=0.506      | 
|COCH-ARM / FISHERS |     P=0.517      P=0.500N     P=0.527N     P=0.701N    |P=0.390      P=0.674N     P=0.674N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.525N     (e)          (e)          (e)         |P=0.628      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/15 (13%)   0/15 (0%)    0/14 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    0/15 (0%)    1/15 (7%)    | 
|POLY-3 RATE (b)    |     2/13.82      0/14.58      0/13.49      0/14.62     |0/12.01      0/10.24      0/12.33      1/12.46      | 
|POLY-3 PERCENT (g) |     14.5%        0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         8.0%         | 
|TERMINAL (d)       |     2/13 (15%)   0/13 (0%)    0/13 (0%)    0/14 (0%)   |0/10 (0%)    0/9 (0%)     0/10 (0%)    1/12 (8%)    | 
|FIRST INCIDENCE    |     183 (T)      ---          ---          ---         |---          ---          ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.152N     P=0.235N     P=0.235N     P=0.219N    |P=0.220      (e)          (e)          P=0.536      | 
|POLY 3             |     P=0.163N     P=0.219N     P=0.236N     P=0.218N    |P=0.202      (e)          (e)          P=0.507      | 
|POLY 1.5           |     P=0.163N     P=0.218N     P=0.235N     P=0.218N    |P=0.195      (e)          (e)          P=0.503      | 
|POLY 6             |     P=0.162N     P=0.220N     P=0.238N     P=0.219N    |P=0.208      (e)          (e)          P=0.512      | 
|LOGISTIC REGRESSION|     P=0.152N     (e)          (e)          (e)         |(e)          (e)          (e)          P=0.536      | 
|COCH-ARM / FISHERS |     P=0.161N     P=0.241N     P=0.259N     P=0.241N    |P=0.185      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.022N*    (e)          (e)          (e)         |P=0.127      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus: Thymocyte                                                                                                                | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/14 (0%)    1/15 (7%)   |2/15 (13%)   0/15 (0%)    0/15 (0%)    2/15 (13%)   | 
|POLY-3 RATE (b)    |     0/13.82      0/14.58      0/13.49      1/15.00     |2/13.21      0/10.24      0/12.33      2/14.46      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         6.7%        |15.1%        0.0%         0.0%         13.8%        | 
|TERMINAL (d)       |     0/13 (0%)    0/13 (0%)    0/13 (0%)    0/14 (0%)   |0/10 (0%)    0/9 (0%)     0/10 (0%)    0/12 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          156         |28           ---          ---          9            | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.197      (e)          (e)          P=0.514     |P=0.423      P=0.271N     P=0.249N     P=0.681      | 
|POLY 3             |     P=0.196      (e)          (e)          P=0.516     |P=0.511      P=0.293N     P=0.246N     P=0.666N     | 
|POLY 1.5           |     P=0.194      (e)          (e)          P=0.514     |P=0.487      P=0.273N     P=0.242N     P=0.672N     | 
|POLY 6             |     P=0.198      (e)          (e)          P=0.519     |P=0.526      P=0.307N     P=0.252N     P=0.663N     | 
|LOGISTIC REGRESSION|     P=0.130      (e)          (e)          P=0.442     |P=0.477      P=0.199N     P=0.253N     P=0.760N     | 
|COCH-ARM / FISHERS |     P=0.186      (e)          (e)          P=0.500     |P=0.422      P=0.241N     P=0.241N     P=0.701N     | 
|ORDER RESTRICTED   |     P=0.136      (e)          (e)          (e)         |P=0.256N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    1/14 (7%)    1/15 (7%)    2/15 (13%)  |0/15 (0%)    0/13 (0%)    5/13 (38%)   11/15 (73%)  | 
|POLY-3 RATE (b)    |     0/13.82      1/13.98      1/14.49      2/14.62     |0/12.01      0/10.10      5/11.63      11/12.46     | 
|POLY-3 PERCENT (g) |     0.0%         7.2%         6.9%         13.7%       |0.0%         0.0%         43.0%        88.3%        | 
|TERMINAL (d)       |     0/13 (0%)    1/13 (8%)    1/14 (7%)    2/14 (14%)  |0/10 (0%)    0/9 (0%)     5/10 (50%)   11/12 (92%)  | 
|FIRST INCIDENCE    |     ---          183 (T)      183 (T)      183 (T)     |---          ---          184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.181      P=0.500      P=0.515      P=0.252     |P<0.001 **   (e)          P=0.022 *    P<0.001 **   | 
|POLY 3             |     P=0.183      P=0.502      P=0.509      P=0.244     |P<0.001 **   (e)          P=0.011 *    P<0.001 **   | 
|POLY 1.5           |     P=0.184      P=0.500      P=0.510      P=0.245     |P<0.001 **   (e)          P=0.010 *    P<0.001 **   | 
|POLY 6             |     P=0.181      P=0.504      P=0.508      P=0.243     |P<0.001 **   (e)          P=0.012 *    P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          P=0.500      P=0.515      P=0.252     |(e)          (e)          P=0.022 *    P<0.001 **   | 
|COCH-ARM / FISHERS |     P=0.169      P=0.483      P=0.500      P=0.241     |P<0.001 **   (e)          P=0.013 *    P<0.001 **   | 
|ORDER RESTRICTED   |     P=0.124      (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicle                                                                                                          | 
|     Depletion Secretory                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/15 (27%)   6/14 (43%)   15/15 (100%) 15/15 (100%)|7/15 (47%)   7/13 (54%)   11/13 (85%)  14/15 (93%)  | 
|POLY-3 RATE (b)    |     4/13.82      6/14.00      15/15.00     15/15.00    |7/12.32      7/10.62      11/12.62     14/14.00     | 
|POLY-3 PERCENT (g) |     28.9%        42.9%        100.0%       100.0%      |56.8%        65.9%        87.2%        100.0%       | 
|TERMINAL (d)       |     4/13 (31%)   5/13 (39%)   14/14 (100%) 14/14 (100%)|5/10 (50%)   6/9 (67%)    10/10 (100%) 12/12 (100%) | 
|FIRST INCIDENCE    |     183 (T)      182          144          156         |171          144          28           28           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.359      P<0.001 **   P<0.001 **  |P=0.015 *    P=0.512      P=0.124      P=0.060      | 
|POLY 3             |     P<0.001 **   P=0.359      P<0.001 **   P<0.001 **  |P=0.002 **   P=0.494      P=0.097      P=0.005 **   | 
|POLY 1.5           |     P<0.001 **   P=0.352      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.516      P=0.088      P=0.003 **   | 
|POLY 6             |     P<0.001 **   P=0.367      P<0.001 **   P<0.001 **  |P=0.003 **   P=0.470      P=0.089      P=0.007 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.386      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.459      P=0.055      P=0.004 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.300      P<0.001 **   P<0.001 **  |P=0.002 **   P=0.500      P=0.043 *    P=0.007 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/18/04                           EXPERIMENT: 97013 TEST: 09                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -         WATER DISINFECTION MODEL (SOD
IUM BR                                                                                                                              
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    2/14 (14%)   12/15 (80%)  15/15 (100%)|2/15 (13%)   2/13 (15%)   11/13 (85%)  13/15 (87%)  | 
|POLY-3 RATE (b)    |     1/13.82      2/13.98      12/14.49     15/15.00    |2/12.01      2/10.10      11/12.62     13/13.46     | 
|POLY-3 PERCENT (g) |     7.2%         14.3%        82.8%        100.0%      |16.7%        19.8%        87.2%        96.6%        | 
|TERMINAL (d)       |     1/13 (8%)    2/13 (15%)   12/14 (86%)  14/14 (100%)|2/10 (20%)   2/9 (22%)    10/10 (100%) 12/12 (100%) | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      156         |184 (T)      184 (T)      28           28           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.500      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.667      P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P=0.504      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.637      P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.501      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.648      P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.508      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.628      P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.500      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.667      P<0.001 **   P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.473      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.644      P<0.001 **   P<0.001 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       80 MG/L      400 MG/L     800 MG/L    |0 MG/L       80 MG/L      400 MG/L     800 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |4/15 (27%)   7/15 (47%)   6/15 (40%)   3/15 (20%)   | 
|POLY-3 RATE (b)    |                                                        |4/12.01      7/10.24      6/12.33      3/12.46      | 
|POLY-3 PERCENT (g) |                                                        |33.3%        68.4%        48.7%        24.1%        | 
|TERMINAL (d)       |                                                        |4/10 (40%)   7/9 (78%)    6/10 (60%)   3/12 (25%)   | 
|FIRST INCIDENCE    |                                                        |184 (T)      184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.088N     P=0.121      P=0.331      P=0.388N     | 
|POLY 3             |                                                        |P=0.156N     P=0.102      P=0.361      P=0.478N     | 
|POLY 1.5           |                                                        |P=0.185N     P=0.140      P=0.366      P=0.492N     | 
|POLY 6             |                                                        |P=0.135N     P=0.080      P=0.350      P=0.465N     | 
|LOGISTIC REGRESSION|                                                        |P=0.088N     P=0.121      P=0.331      P=0.388N     | 
|COCH-ARM / FISHERS |                                                        |P=0.233N     P=0.225      P=0.350      P=0.500N     | 
|ORDER RESTRICTED   |                                                        |P=0.143N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
                                                                                                                                   
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.