National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/11687

TDMS Study 97013-96 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 10/08/03       
EXPERIMENT: 97013 TEST: 96                                                                                     TIME: 15:30:51       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-65406                              ROUTE: DOSED WATER                                             NTP C#: 97013J       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
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                                                             FINAL/MICE                                                             
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 10/08/03       
EXPERIMENT: 97013 TEST: 96                                                                                     TIME: 15:30:51       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-65406                              ROUTE: DOSED WATER                                             NTP C#: 97013J       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF     WATER DISINFECTION MODEL (BROMODICHLOR                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Kidney                                 Nephropathy                                                                                  
Kidney: Renal Tubule                   Degeneration                                                                                 
                                       Vacuolization Cytoplasmic                                                                    
Liver                                  Inflammation                                                                                 
                                       Necrosis                                                                                     
Liver: Hepatocyte                      Fatty Change                                                                                 
Spleen                                 Atrophy                                                                                      
Thymus                                 Atrophy                                                                                      
                                       Cyst                                                                                         
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Kidney                                 Casts Protein                                                                                
                                       Nephropathy                                                                                  
Liver: Hepatocyte                      Fatty Change                                                                                 
===============================================================                                                                     
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODI
CHLOR                                                                                                                               
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   4/10 (40%)   2/10 (20%)   0/10 (0%)   |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     2/9.42       4/10.00      2/9.82       0/7.80      |0/9.90       0/9.23       0/10.00      0/8.48       | 
|POLY-3 PERCENT (g) |     21.2%        40.0%        20.4%        0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/9 (22%)    4/10 (40%)   2/9 (22%)    0/7 (0%)    |0/9 (0%)     0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     296 (T)      296 (T)      296 (T)      ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.140N     P=0.371      P=0.709      P=0.290N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.132N     P=0.348      P=0.688N     P=0.272N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.120N     P=0.336      P=0.693N     P=0.260N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.139N     P=0.362      P=0.684N     P=0.280N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.140N     P=0.371      P=0.709      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.091N     P=0.314      P=0.709N     P=0.237N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.104N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   2/10 (20%)   3/10 (30%)   2/10 (20%)  |9/10 (90%)   10/10 (100%) 10/10 (100%) 8/10 (80%)   | 
|POLY-3 RATE (b)    |     2/9.42       2/10.00      3/9.82       2/7.80      |9/10.00      10/10.00     10/10.00     8/9.01       | 
|POLY-3 PERCENT (g) |     21.2%        20.0%        30.6%        25.7%       |90.0%        100.0%       100.0%       88.8%        | 
|TERMINAL (d)       |     2/9 (22%)    2/10 (20%)   3/9 (33%)    2/7 (29%)   |8/9 (89%)    9/9 (100%)   10/10 (100%) 7/8 (88%)    | 
|FIRST INCIDENCE    |     296 (T)      296 (T)      296 (T)      296 (T)     |287          183          297 (T)      231          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.435      P=0.667N     P=0.500      P=0.611     |P=0.542N     P=0.488      P=0.749      P=0.686      | 
|POLY 3             |     P=0.454      P=0.680N     P=0.521      P=0.633     |P=0.577N     P=0.500      P=0.500      P=0.735N     | 
|POLY 1.5           |     P=0.484      P=0.689N     P=0.513      P=0.651     |P=0.545N     P=0.500      P=0.500      P=0.718N     | 
|POLY 6             |     P=0.433      P=0.671N     P=0.526      P=0.620     |P=0.579N     P=0.500      P=0.500      P=0.737N     | 
|LOGISTIC REGRESSION|     P=0.435      P=0.667N     P=0.500      P=0.611     |P=0.501N     (e)          P=0.749      P=0.773N     | 
|COCH-ARM / FISHERS |     P=0.576      P=0.709N     P=0.500      P=0.709N    |P=0.239N     P=0.500      P=0.500      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.573      (e)          (e)          (e)         |P=0.363N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Casts Protein                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)   |8/10 (80%)   1/10 (10%)   5/10 (50%)   3/10 (30%)   | 
|POLY-3 RATE (b)    |     0/9.42       0/10.00      1/10.00      0/7.80      |8/9.90       1/9.23       5/10.00      3/9.01       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         10.0%        0.0%        |80.8%        10.8%        50.0%        33.3%        | 
|TERMINAL (d)       |     0/9 (0%)     0/10 (0%)    0/9 (0%)     0/7 (0%)    |8/9 (89%)    1/9 (11%)    5/10 (50%)   2/8 (25%)    | 
|FIRST INCIDENCE    |     ---          ---          277          ---         |297 (T)      297 (T)      297 (T)      231          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.671      (e)          P=0.521      (e)         |P=0.146N     P=0.003N**   P=0.098N     P=0.073N     | 
|POLY 3             |     P=0.590      (e)          P=0.512      (e)         |P=0.094N     P<0.001N**   P=0.164N     P=0.040N*    | 
|POLY 1.5           |     P=0.620      (e)          P=0.507      (e)         |P=0.098N     P<0.001N**   P=0.169N     P=0.040N*    | 
|POLY 6             |     P=0.567      (e)          P=0.517      (e)         |P=0.088N     P<0.001N**   P=0.155N     P=0.037N*    | 
|LOGISTIC REGRESSION|     P=0.729      (e)          P=0.421      (e)         |P=0.142N     P=0.003N**   P=0.098N     P=0.053N     | 
|COCH-ARM / FISHERS |     P=0.696      (e)          P=0.500      (e)         |P=0.107N     P=0.003N**   P=0.175N     P=0.035N*    | 
|ORDER RESTRICTED   |     P=0.396      (e)          (e)          (e)         |P=0.012N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)   |1/10 (10%)   4/10 (40%)   0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     1/9.42       0/10.00      0/9.82       0/7.80      |1/9.90       4/9.23       0/10.00      1/8.48       | 
|POLY-3 PERCENT (g) |     10.6%        0.0%         0.0%         0.0%        |10.1%        43.3%        0.0%         11.8%        | 
|TERMINAL (d)       |     1/9 (11%)    0/10 (0%)    0/9 (0%)     0/7 (0%)    |1/9 (11%)    4/9 (44%)    0/10 (0%)    1/8 (13%)    | 
|FIRST INCIDENCE    |     296 (T)      ---          ---          ---         |297 (T)      297 (T)      ---          297 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.334N     P=0.479N     P=0.500N     P=0.550N    |P=0.360N     P=0.153      P=0.479N     P=0.741      | 
|POLY 3             |     P=0.281N     P=0.488N     P=0.492N     P=0.537N    |P=0.360N     P=0.123      P=0.498N     P=0.726      | 
|POLY 1.5           |     P=0.289N     P=0.493N     P=0.495N     P=0.528N    |P=0.353N     P=0.131      P=0.499N     P=0.732      | 
|POLY 6             |     P=0.276N     P=0.483N     P=0.489N     P=0.543N    |P=0.364N     P=0.120      P=0.496N     P=0.721      | 
|LOGISTIC REGRESSION|     P=0.334N     (e)          (e)          (e)         |P=0.360N     P=0.153      (e)          P=0.741      | 
|COCH-ARM / FISHERS |     P=0.304N     P=0.500N     P=0.500N     P=0.500N    |P=0.327N     P=0.152      P=0.500N     P=0.763N     | 
|ORDER RESTRICTED   |     P=0.155N     (e)          (e)          (e)         |P=0.163N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/10 (50%)   4/10 (40%)   9/10 (90%)   8/10 (80%)  |3/10 (30%)   1/10 (10%)   8/10 (80%)   0/10 (0%)    | 
|POLY-3 RATE (b)    |     5/9.42       4/10.00      9/9.82       8/8.61      |3/10.00      1/10.00      8/10.00      0/8.48       | 
|POLY-3 PERCENT (g) |     53.1%        40.0%        91.7%        93.0%       |30.0%        10.0%        80.0%        0.0%         | 
|TERMINAL (d)       |     5/9 (56%)    4/10 (40%)   9/9 (100%)   7/7 (100%)  |2/9 (22%)    0/9 (0%)     8/10 (80%)   0/8 (0%)     | 
|FIRST INCIDENCE    |     296 (T)      296 (T)      296 (T)      170         |287          183          297 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.003 **   P=0.416N     P=0.049 *    P=0.041 *   |P=0.302N     P=0.315N     P=0.078      P=0.147N     | 
|POLY 3             |     P=0.007 **   P=0.453N     P=0.066      P=0.068     |P=0.355N     P=0.292N     P=0.024 *    P=0.128N     | 
|POLY 1.5           |     P=0.011 *    P=0.472N     P=0.064      P=0.087     |P=0.316N     P=0.292N     P=0.024 *    P=0.121N     | 
|POLY 6             |     P=0.005 **   P=0.432N     P=0.066      P=0.057     |P=0.391N     P=0.292N     P=0.024 *    P=0.135N     | 
|LOGISTIC REGRESSION|     P=0.010 *    P=0.416N     P=0.049 *    P=0.066     |P=0.239N     (e)          P=0.078      P=0.127N     | 
|COCH-ARM / FISHERS |     P=0.046 *    P=0.500N     P=0.070      P=0.175     |P=0.242N     P=0.291N     P=0.035 *    P=0.105N     | 
|ORDER RESTRICTED   |     P=0.013 *    (e)          (e)          (e)         |P=0.015N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    6/10 (60%)   10/10 (100%)|0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/9.42       0/10.00      6/9.82       10/10.00    |0/9.90       0/9.23       0/10.00      0/8.48       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         61.1%        100.0%      |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/9 (0%)     0/10 (0%)    6/9 (67%)    7/7 (100%)  |0/9 (0%)     0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          296 (T)      95          |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          P=0.008 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   (e)          P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   (e)          P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   (e)          P<0.001 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          P=0.008 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          P=0.005 **   P<0.001 **  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   0/10 (0%)    3/10 (30%)   2/10 (20%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     1/9.42       0/10.00      3/9.82       2/7.80      |0/9.90       0/9.23       0/10.00      0/8.48       | 
|POLY-3 PERCENT (g) |     10.6%        0.0%         30.6%        25.7%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/9 (11%)    0/10 (0%)    3/9 (33%)    2/7 (29%)   |0/9 (0%)     0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     296 (T)      ---          296 (T)      296 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.141      P=0.479N     P=0.291      P=0.407     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.145      P=0.488N     P=0.307      P=0.431     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.164      P=0.493N     P=0.301      P=0.449     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.132      P=0.483N     P=0.311      P=0.420     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.141      (e)          P=0.291      P=0.407     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.227      P=0.500N     P=0.291      P=0.500     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.162      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/10 (100%) 5/10 (50%)   0/10 (0%)    0/10 (0%)   |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     10/10.00     5/10.00      0/9.82       0/7.80      |0/9.90       0/9.23       0/10.00      0/8.48       | 
|POLY-3 PERCENT (g) |     100.0%       50.0%        0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     9/9 (100%)   5/10 (50%)   0/9 (0%)     0/7 (0%)    |0/9 (0%)     0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     221          296 (T)      ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001N**   P=0.016N*    P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001N**   P=0.008N**   P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001N**   P=0.008N**   P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001N**   P=0.008N**   P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001N**   P=0.016N*    P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001N**   P=0.016N*    P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001N**   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%)  |2/10 (20%)   1/10 (10%)   0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/9.42       0/10.00      0/9.82       1/7.80      |2/10.00      1/10.00      0/10.00      1/9.01       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         12.8%       |20.0%        10.0%        0.0%         11.1%        | 
|TERMINAL (d)       |     0/9 (0%)     0/10 (0%)    0/9 (0%)     1/7 (14%)   |1/9 (11%)    0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          296 (T)     |287          183          ---          231          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.158      (e)          (e)          P=0.450     |P=0.398N     P=0.512N     P=0.228N     P=0.551N     | 
|POLY 3             |     P=0.172      (e)          (e)          P=0.462     |P=0.369N     P=0.500N     P=0.227N     P=0.537N     | 
|POLY 1.5           |     P=0.179      (e)          (e)          P=0.472     |P=0.368N     P=0.500N     P=0.227N     P=0.534N     | 
|POLY 6             |     P=0.168      (e)          (e)          P=0.456     |P=0.369N     P=0.500N     P=0.227N     P=0.538N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.450     |P=0.191N     (e)          (e)          P=0.462N     | 
|COCH-ARM / FISHERS |     P=0.196      (e)          (e)          P=0.500     |P=0.361N     P=0.500N     P=0.237N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.092      (e)          (e)          (e)         |P=0.245N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   2/10 (20%)   0/10 (0%)    0/10 (0%)   |2/10 (20%)   4/10 (40%)   4/10 (40%)   2/10 (20%)   | 
|POLY-3 RATE (b)    |     1/9.42       2/10.00      0/9.82       0/7.80      |2/9.90       4/9.23       4/10.00      2/8.48       | 
|POLY-3 PERCENT (g) |     10.6%        20.0%        0.0%         0.0%        |20.2%        43.3%        40.0%        23.6%        | 
|TERMINAL (d)       |     1/9 (11%)    2/10 (20%)   0/9 (0%)     0/7 (0%)    |2/9 (22%)    4/9 (44%)    4/10 (40%)   2/8 (25%)    | 
|FIRST INCIDENCE    |     296 (T)      296 (T)      ---          ---         |297 (T)      297 (T)      297 (T)      297 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.222N     P=0.539      P=0.500N     P=0.550N    |P=0.565N     P=0.314      P=0.371      P=0.665      | 
|POLY 3             |     P=0.191N     P=0.522      P=0.492N     P=0.537N    |P=0.569      P=0.279      P=0.322      P=0.644      | 
|POLY 1.5           |     P=0.190N     P=0.513      P=0.495N     P=0.528N    |P=0.581N     P=0.291      P=0.320      P=0.656      | 
|POLY 6             |     P=0.191N     P=0.531      P=0.489N     P=0.543N    |P=0.554      P=0.274      P=0.327      P=0.636      | 
|LOGISTIC REGRESSION|     P=0.222N     P=0.539      (e)          (e)         |P=0.565N     P=0.314      P=0.371      P=0.665      | 
|COCH-ARM / FISHERS |     P=0.181N     P=0.500      P=0.500N     P=0.500N    |P=0.500N     P=0.314      P=0.314      P=0.709N     | 
|ORDER RESTRICTED   |     P=0.208N     (e)          (e)          (e)         |P=0.386      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/10 (90%)   5/10 (50%)   7/10 (70%)   6/10 (60%)  |8/10 (80%)   7/10 (70%)   8/10 (80%)   7/10 (70%)   | 
|POLY-3 RATE (b)    |     9/9.42       5/10.00      7/9.82       6/8.61      |8/9.90       7/9.23       8/10.00      7/8.48       | 
|POLY-3 PERCENT (g) |     95.6%        50.0%        71.3%        69.7%       |80.8%        75.8%        80.0%        82.6%        | 
|TERMINAL (d)       |     9/9 (100%)   5/10 (50%)   7/9 (78%)    5/7 (71%)   |8/9 (89%)    7/9 (78%)    8/10 (80%)   7/8 (88%)    | 
|FIRST INCIDENCE    |     296 (T)      296 (T)      296 (T)      170         |297 (T)      297 (T)      297 (T)      297 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.571N     P=0.029N*    P=0.233N     P=0.453N    |P=0.601      P=0.500N     P=0.539N     P=0.741N     | 
|POLY 3             |     P=0.325N     P=0.026N*    P=0.194N     P=0.180N    |P=0.534      P=0.612N     P=0.691N     P=0.691      | 
|POLY 1.5           |     P=0.305N     P=0.037N*    P=0.231N     P=0.182N    |P=0.567      P=0.575N     P=0.696N     P=0.705N     | 
|POLY 6             |     P=0.341N     P=0.018N*    P=0.161N     P=0.171N    |P=0.506      P=0.631N     P=0.680N     P=0.663      | 
|LOGISTIC REGRESSION|     P=0.410N     P=0.029N*    P=0.233N     P=0.311N    |P=0.601      P=0.500N     P=0.539N     P=0.741N     | 
|COCH-ARM / FISHERS |     P=0.229N     P=0.070N     P=0.291N     P=0.152N    |P=0.451N     P=0.500N     P=0.709N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.094N     (e)          (e)          (e)         |P=0.642      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    2/10 (20%)  |3/10 (30%)   2/10 (20%)   1/10 (10%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/9.42       0/10.00      0/9.82       2/9.57      |3/10.00      2/9.23       1/10.00      1/9.47       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         20.9%       |30.0%        21.7%        10.0%        10.6%        | 
|TERMINAL (d)       |     0/9 (0%)     0/10 (0%)    0/9 (0%)     0/7 (0%)    |2/9 (22%)    2/9 (22%)    1/10 (10%)   0/8 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          95          |287          297 (T)      297 (T)      57           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.043 *    (e)          (e)          P=0.228     |P=0.216N     P=0.510N     P=0.272N     P=0.347N     | 
|POLY 3             |     P=0.037 *    (e)          (e)          P=0.230     |P=0.189N     P=0.539N     P=0.292N     P=0.312N     | 
|POLY 1.5           |     P=0.038 *    (e)          (e)          P=0.229     |P=0.187N     P=0.526N     P=0.292N     P=0.304N     | 
|POLY 6             |     P=0.036 *    (e)          (e)          P=0.229     |P=0.192N     P=0.549N     P=0.292N     P=0.323N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.079N     P=0.535N     P=0.272N     P=0.100N     | 
|COCH-ARM / FISHERS |     P=0.043 *    (e)          (e)          P=0.237     |P=0.180N     P=0.500N     P=0.291N     P=0.291N     | 
|ORDER RESTRICTED   |     P=0.024 *    (e)          (e)          (e)         |P=0.212N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Fatty Change                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/10 (80%)   4/10 (40%)   3/10 (30%)   4/10 (40%)  |2/10 (20%)   2/10 (20%)   3/10 (30%)   6/10 (60%)   | 
|POLY-3 RATE (b)    |     8/10.00      4/10.00      3/10.00      4/8.22      |2/9.90       2/10.00      3/10.00      6/8.48       | 
|POLY-3 PERCENT (g) |     80.0%        40.0%        30.0%        48.7%       |20.2%        20.0%        30.0%        70.8%        | 
|TERMINAL (d)       |     7/9 (78%)    4/10 (40%)   2/9 (22%)    3/7 (43%)   |2/9 (22%)    1/9 (11%)    3/10 (30%)   6/8 (75%)    | 
|FIRST INCIDENCE    |     221          296 (T)      277          246         |297 (T)      183          297 (T)      297 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.234N     P=0.070N     P=0.060N     P=0.258N    |P=0.020 *    P=0.700      P=0.553      P=0.051      | 
|POLY 3             |     P=0.131N     P=0.077N     P=0.024N*    P=0.182N    |P=0.014 *    P=0.699N     P=0.505      P=0.031 *    | 
|POLY 1.5           |     P=0.119N     P=0.077N     P=0.024N*    P=0.147N    |P=0.016 *    P=0.700N     P=0.502      P=0.038 *    | 
|POLY 6             |     P=0.137N     P=0.077N     P=0.024N*    P=0.201N    |P=0.012 *    P=0.696N     P=0.509      P=0.027 *    | 
|LOGISTIC REGRESSION|     P=0.116N     P=0.070N     (e)          P=0.141N    |P=0.024 *    P=0.562N     P=0.553      P=0.051      | 
|COCH-ARM / FISHERS |     P=0.090N     P=0.085N     P=0.035N*    P=0.085N    |P=0.030 *    P=0.709N     P=0.500      P=0.085      | 
|ORDER RESTRICTED   |     P=0.057N     (e)          (e)          (e)         |P=0.013 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/10 (90%)   10/10 (100%) 10/10 (100%) 9/10 (90%)  |9/10 (90%)   9/10 (90%)   10/10 (100%) 8/10 (80%)   | 
|POLY-3 RATE (b)    |     9/9.42       10/10.00     10/10.00     9/9.19      |9/9.90       9/9.23       10/10.00     8/8.48       | 
|POLY-3 PERCENT (g) |     95.6%        100.0%       100.0%       97.9%       |90.9%        97.5%        100.0%       94.4%        | 
|TERMINAL (d)       |     9/9 (100%)   10/10 (100%) 9/9 (100%)   7/7 (100%)  |9/9 (100%)   9/9 (100%)   10/10 (100%) 8/8 (100%)   | 
|FIRST INCIDENCE    |     296 (T)      296 (T)      277          95          |297 (T)      297 (T)      297 (T)      297 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.054      P=1.000      P=0.521      P=0.227     |P=1.000      P=1.000      P=1.000      P=1.000      | 
|POLY 3             |     P=0.836      P=0.909      P=0.909      P=0.946     |P=0.559      P=0.652      P=0.541      P=0.743      | 
|POLY 1.5           |     P=0.763      P=0.699      P=0.699      P=0.838     |P=0.637      P=0.699      P=0.520      P=0.781      | 
|POLY 6             |     P=0.997      P=1.000      P=1.000      P=1.000     |P=0.471      P=0.630      P=0.586      P=0.717      | 
|LOGISTIC REGRESSION|     P=0.322      P=1.000      (e)          P=0.540     |P=1.000      P=1.000      P=1.000      P=1.000      | 
|COCH-ARM / FISHERS |     P=0.597N     P=0.500      P=0.500      P=0.763N    |P=0.361N     P=0.763N     P=0.500      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.231      (e)          (e)          (e)         |P=0.339      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   0/10 (0%)    0/10 (0%)    2/10 (20%)  |1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     1/9.42       0/10.00      0/9.82       2/9.03      |1/10.00      0/9.23       0/10.00      0/8.48       | 
|POLY-3 PERCENT (g) |     10.6%        0.0%         0.0%         22.1%       |10.0%        0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/9 (11%)    0/10 (0%)    0/9 (0%)     0/7 (0%)    |0/9 (0%)     0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     296 (T)      ---          ---          170         |287          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.205      P=0.479N     P=0.500N     P=0.446     |P=0.326N     P=0.521N     P=0.500N     P=0.545N     | 
|POLY 3             |     P=0.227      P=0.488N     P=0.492N     P=0.485     |P=0.279N     P=0.516N     P=0.500N     P=0.533N     | 
|POLY 1.5           |     P=0.229      P=0.493N     P=0.495N     P=0.482     |P=0.285N     P=0.511N     P=0.500N     P=0.526N     | 
|POLY 6             |     P=0.226      P=0.483N     P=0.489N     P=0.493     |P=0.273N     P=0.520N     P=0.500N     P=0.539N     | 
|LOGISTIC REGRESSION|     P=0.498      (e)          (e)          P=0.670     |P=0.300N     P=0.486N     (e)          P=0.513N     | 
|COCH-ARM / FISHERS |     P=0.239      P=0.500N     P=0.500N     P=0.500     |P=0.304N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.106      (e)          (e)          (e)         |P=0.151N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |3/10 (30%)   2/9 (22%)    1/10 (10%)   2/10 (20%)   | 
|POLY-3 RATE (b)    |                                                        |3/10.00      2/8.23       1/10.00      2/9.01       | 
|POLY-3 PERCENT (g) |                                                        |30.0%        24.3%        10.0%        22.2%        | 
|TERMINAL (d)       |                                                        |2/9 (22%)    2/8 (25%)    1/10 (10%)   1/8 (13%)    | 
|FIRST INCIDENCE    |                                                        |287          297 (T)      297 (T)      231          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.434N     P=0.556N     P=0.272N     P=0.563N     | 
|POLY 3             |                                                        |P=0.400N     P=0.595N     P=0.292N     P=0.551N     | 
|POLY 1.5           |                                                        |P=0.401N     P=0.581N     P=0.292N     P=0.547N     | 
|POLY 6             |                                                        |P=0.398N     P=0.606N     P=0.292N     P=0.552N     | 
|LOGISTIC REGRESSION|                                                        |P=0.387N     P=0.596N     P=0.272N     P=0.503N     | 
|COCH-ARM / FISHERS |                                                        |P=0.380N     P=0.556N     P=0.291N     P=0.500N     | 
|ORDER RESTRICTED   |                                                        |P=0.367N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/10 (40%)   3/9 (33%)    3/10 (30%)   3/10 (30%)  |1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     4/10.00      3/9.00       3/9.82       3/7.80      |1/9.90       0/9.23       0/10.00      0/8.48       | 
|POLY-3 PERCENT (g) |     40.0%        33.3%        30.6%        38.5%       |10.1%        0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     3/9 (33%)    3/9 (33%)    3/9 (33%)    3/7 (43%)   |1/9 (11%)    0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     221          296 (T)      296 (T)      296 (T)     |297 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.589N     P=0.500N     P=0.500N     P=0.651N    |P=0.314N     P=0.500N     P=0.479N     P=0.523N     | 
|POLY 3             |     P=0.537N     P=0.566N     P=0.511N     P=0.655N    |P=0.280N     P=0.514N     P=0.498N     P=0.531N     | 
|POLY 1.5           |     P=0.505N     P=0.566N     P=0.506N     P=0.612N    |P=0.286N     P=0.510N     P=0.499N     P=0.525N     | 
|POLY 6             |     P=0.563N     P=0.566N     P=0.521N     P=0.667     |P=0.275N     P=0.516N     P=0.496N     P=0.535N     | 
|LOGISTIC REGRESSION|     P=0.498N     P=0.500N     P=0.577N     P=0.588N    |P=0.314N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.410N     P=0.570N     P=0.500N     P=0.500N    |P=0.304N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.622N     (e)          (e)          (e)         |P=0.149N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     0/0 (0%)     0/0 (0%)     2/2 (100%)  |0/0 (0%)     0/0 (0%)     0/1 (0%)     0/0 (0%)     | 
|POLY-3 RATE (b)    |     0/0.00       0/0.00       0/0.00       2/2.00      |0/0.00       0/0.00       0/1.00       0/0.00       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         100.0%      |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     2/2 (100%)  |0/0 (0%)     0/0 (0%)     0/1 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          296 (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)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    3/10 (30%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/9.42       0/10.00      0/9.82       3/10.00     |0/9.90       0/9.23       0/10.00      1/9.47       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         30.0%       |0.0%         0.0%         0.0%         10.6%        | 
|TERMINAL (d)       |     0/9 (0%)     0/10 (0%)    0/9 (0%)     0/7 (0%)    |0/9 (0%)     0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          95          |---          ---          ---          57           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.010 *    (e)          (e)          P=0.111     |P=0.199      (e)          (e)          P=0.500      | 
|POLY 3             |     P=0.006 **   (e)          (e)          P=0.106     |P=0.196      (e)          (e)          P=0.491      | 
|POLY 1.5           |     P=0.006 **   (e)          (e)          P=0.102     |P=0.198      (e)          (e)          P=0.495      | 
|POLY 6             |     P=0.006 **   (e)          (e)          P=0.111     |P=0.195      (e)          (e)          P=0.488      | 
|LOGISTIC REGRESSION|     P=0.091      (e)          (e)          P=0.310     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.010 *    (e)          (e)          P=0.105     |P=0.196      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.004 **   (e)          (e)          (e)         |P=0.112      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)   |2/10 (20%)   1/10 (10%)   0/10 (0%)    2/10 (20%)   | 
|POLY-3 RATE (b)    |     1/10.00      0/10.00      0/9.82       0/7.80      |2/10.00      1/10.00      0/10.00      2/9.01       | 
|POLY-3 PERCENT (g) |     10.0%        0.0%         0.0%         0.0%        |20.0%        10.0%        0.0%         22.2%        | 
|TERMINAL (d)       |     0/9 (0%)     0/10 (0%)    0/9 (0%)     0/7 (0%)    |1/9 (11%)    0/9 (0%)     0/10 (0%)    1/8 (13%)    | 
|FIRST INCIDENCE    |     221          ---          ---          ---         |287          183          ---          231          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.328N     P=0.500N     P=0.500N     P=0.545N    |P=0.555      P=0.512N     P=0.228N     P=0.643      | 
|POLY 3             |     P=0.273N     P=0.500N     P=0.504N     P=0.549N    |P=0.573      P=0.500N     P=0.227N     P=0.663      | 
|POLY 1.5           |     P=0.284N     P=0.500N     P=0.502N     P=0.535N    |P=0.575      P=0.500N     P=0.227N     P=0.667      | 
|POLY 6             |     P=0.265N     P=0.500N     P=0.507N     P=0.559N    |P=0.573      P=0.500N     P=0.227N     P=0.663      | 
|LOGISTIC REGRESSION|     P=0.102N     (e)          (e)          P=0.354N    |P=0.513N     (e)          (e)          P=0.708N     | 
|COCH-ARM / FISHERS |     P=0.304N     P=0.500N     P=0.500N     P=0.500N    |P=0.596      P=0.500N     P=0.237N     P=0.709N     | 
|ORDER RESTRICTED   |     P=0.169N     (e)          (e)          (e)         |P=0.352      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Hyperkeratosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)   |0/10 (0%)    1/10 (10%)   0/10 (0%)    2/10 (20%)   | 
|POLY-3 RATE (b)    |     0/9.42       0/10.00      0/9.82       0/7.80      |0/9.90       1/10.00      0/10.00      2/10.00      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         10.0%        0.0%         20.0%        | 
|TERMINAL (d)       |     0/9 (0%)     0/10 (0%)    0/9 (0%)     0/7 (0%)    |0/9 (0%)     0/9 (0%)     0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          183          ---          57           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.131      P=0.500      (e)          P=0.228      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.134      P=0.502      (e)          P=0.229      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.133      P=0.501      (e)          P=0.228      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.135      P=0.504      (e)          P=0.231      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.132      P=0.500      (e)          P=0.237      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.067      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   1/10 (10%)   1/10 (10%)   1/10 (10%)  |0/10 (0%)    2/10 (20%)   0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     1/10.00      1/10.00      1/9.82       1/8.22      |0/9.90       2/9.23       0/10.00      0/8.48       | 
|POLY-3 PERCENT (g) |     10.0%        10.0%        10.2%        12.2%       |0.0%         21.7%        0.0%         0.0%         | 
|TERMINAL (d)       |     0/9 (0%)     1/10 (10%)   1/9 (11%)    0/7 (0%)    |0/9 (0%)     2/9 (22%)    0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     221          296 (T)      296 (T)      246         |---          297 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.572      P=0.749N     P=0.760      P=0.722     |P=0.423N     P=0.233      (e)          (e)          | 
|POLY 3             |     P=0.563      P=0.760      P=0.756      P=0.716     |P=0.430N     P=0.209      (e)          (e)          | 
|POLY 1.5           |     P=0.580      P=0.760      P=0.758      P=0.727     |P=0.424N     P=0.215      (e)          (e)          | 
|POLY 6             |     P=0.555      P=0.760      P=0.753      P=0.710     |P=0.432N     P=0.207      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.507N     P=0.749N     P=0.592      P=0.682N    |(e)          P=0.233      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.639      P=0.763N     P=0.763N     P=0.763N    |P=0.403N     P=0.237      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.681      (e)          (e)          (e)         |P=0.246N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   2/10 (20%)   1/10 (10%)   3/10 (30%)  |                                                    | 
|POLY-3 RATE (b)    |     2/9.42       2/10.00      1/9.82       3/8.22      |                                                    | 
|POLY-3 PERCENT (g) |     21.2%        20.0%        10.2%        36.5%       |                                                    | 
|TERMINAL (d)       |     2/9 (22%)    2/10 (20%)   1/9 (11%)    2/7 (29%)   |                                                    | 
|FIRST INCIDENCE    |     296 (T)      296 (T)      296 (T)      246         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.280      P=0.667N     P=0.500N     P=0.392     |                                                    | 
|POLY 3             |     P=0.345      P=0.680N     P=0.485N     P=0.432     |                                                    | 
|POLY 1.5           |     P=0.354      P=0.689N     P=0.490N     P=0.443     |                                                    | 
|POLY 6             |     P=0.343      P=0.671N     P=0.481N     P=0.433     |                                                    | 
|LOGISTIC REGRESSION|     P=0.333      P=0.667N     P=0.500N     P=0.427     |                                                    | 
|COCH-ARM / FISHERS |     P=0.395      P=0.709N     P=0.500N     P=0.500     |                                                    | 
|ORDER RESTRICTED   |     P=0.279      (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    1/10 (10%)   3/10 (30%)  |2/10 (20%)   1/9 (11%)    0/10 (0%)    2/10 (20%)   | 
|POLY-3 RATE (b)    |     0/9.42       0/10.00      1/10.00      3/10.00     |2/10.00      1/9.00       0/10.00      2/10.00      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         10.0%        30.0%       |20.0%        11.1%        0.0%         20.0%        | 
|TERMINAL (d)       |     0/9 (0%)     0/10 (0%)    0/9 (0%)     0/7 (0%)    |1/9 (11%)    1/9 (11%)    0/10 (0%)    0/8 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          277          95          |287          297 (T)      ---          57           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.014 *    (e)          P=0.521      P=0.111     |P=0.564      P=0.512N     P=0.228N     P=0.652      | 
|POLY 3             |     P=0.014 *    (e)          P=0.512      P=0.106     |P=0.605      P=0.538N     P=0.227N     P=0.702      | 
|POLY 1.5           |     P=0.014 *    (e)          P=0.507      P=0.102     |P=0.605      P=0.538N     P=0.227N     P=0.702      | 
|POLY 6             |     P=0.015 *    (e)          P=0.517      P=0.111     |P=0.605      P=0.538N     P=0.227N     P=0.702      | 
|LOGISTIC REGRESSION|     P=0.133      (e)          P=0.421      P=0.310     |(e)          P=0.512N     (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.016 *    (e)          P=0.500      P=0.105     |P=0.607      P=0.542N     P=0.237N     P=0.709N     | 
|ORDER RESTRICTED   |     P=0.016 *    (e)          (e)          (e)         |P=0.401N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/10 (80%)   7/10 (70%)   3/10 (30%)   4/10 (40%)  |7/10 (70%)   6/9 (67%)    8/10 (80%)   8/10 (80%)   | 
|POLY-3 RATE (b)    |     8/9.42       7/10.00      3/10.00      4/9.57      |7/10.00      6/9.00       8/10.00      8/8.48       | 
|POLY-3 PERCENT (g) |     85.0%        70.0%        30.0%        41.8%       |70.0%        66.7%        80.0%        94.4%        | 
|TERMINAL (d)       |     8/9 (89%)    7/10 (70%)   2/9 (22%)    2/7 (29%)   |6/9 (67%)    6/9 (67%)    8/10 (80%)   8/8 (100%)   | 
|FIRST INCIDENCE    |     296 (T)      296 (T)      277          95          |287          297 (T)      297 (T)      297 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.131N     P=0.333N     P=0.045N*    P=0.243N    |P=0.158      P=0.509N     P=0.631      P=0.311      | 
|POLY 3             |     P=0.023N*    P=0.405N     P=0.012N*    P=0.055N    |P=0.129      P=0.626N     P=0.500      P=0.226      | 
|POLY 1.5           |     P=0.025N*    P=0.444N     P=0.016N*    P=0.062N    |P=0.164      P=0.626N     P=0.500      P=0.283      | 
|POLY 6             |     P=0.023N*    P=0.363N     P=0.008N**   P=0.051N    |P=0.103      P=0.626N     P=0.500      P=0.177      | 
|LOGISTIC REGRESSION|     P=0.015N*    P=0.333N     P=0.024N*    P=0.058N    |P=0.091      P=0.509N     P=0.631      P=0.170      | 
|COCH-ARM / FISHERS |     P=0.034N*    P=0.500N     P=0.035N*    P=0.085N    |P=0.339      P=0.630N     P=0.500      P=0.500      | 
|ORDER RESTRICTED   |     P=0.015N*    (e)          (e)          (e)         |P=0.151      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |2/10 (20%)   1/10 (10%)   2/10 (20%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |                                                        |2/9.90       1/9.23       2/10.00      1/8.48       | 
|POLY-3 PERCENT (g) |                                                        |20.2%        10.8%        20.0%        11.8%        | 
|TERMINAL (d)       |                                                        |2/9 (22%)    1/9 (11%)    2/10 (20%)   1/8 (13%)    | 
|FIRST INCIDENCE    |                                                        |297 (T)      297 (T)      297 (T)      297 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.480N     P=0.500N     P=0.667N     P=0.543N     | 
|POLY 3             |                                                        |P=0.482N     P=0.525N     P=0.699N     P=0.556N     | 
|POLY 1.5           |                                                        |P=0.477N     P=0.517N     P=0.700N     P=0.545N     | 
|POLY 6             |                                                        |P=0.486N     P=0.529N     P=0.696N     P=0.563N     | 
|LOGISTIC REGRESSION|                                                        |P=0.480N     P=0.500N     P=0.667N     P=0.543N     | 
|COCH-ARM / FISHERS |                                                        |P=0.441N     P=0.500N     P=0.709N     P=0.500N     | 
|ORDER RESTRICTED   |                                                        |P=0.507N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/08/03                           EXPERIMENT: 97013 TEST: 96                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 43 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/L       175 MG/L     350 MG/L     700 MG/L    |0 MG/L       175 MG/L     350 MG/L     700 MG/L     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |8/10 (80%)   8/10 (80%)   8/10 (80%)   6/10 (60%)   | 
|POLY-3 RATE (b)    |                                                        |8/9.90       8/9.23       8/10.00      6/8.48       | 
|POLY-3 PERCENT (g) |                                                        |80.8%        86.6%        80.0%        70.8%        | 
|TERMINAL (d)       |                                                        |8/9 (89%)    8/9 (89%)    8/10 (80%)   6/8 (75%)    | 
|FIRST INCIDENCE    |                                                        |297 (T)      297 (T)      297 (T)      297 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.286N     P=0.767      P=0.539N     P=0.457N     | 
|POLY 3             |                                                        |P=0.356N     P=0.606      P=0.691N     P=0.518N     | 
|POLY 1.5           |                                                        |P=0.328N     P=0.641      P=0.696N     P=0.475N     | 
|POLY 6             |                                                        |P=0.378N     P=0.589      P=0.680N     P=0.552N     | 
|LOGISTIC REGRESSION|                                                        |P=0.286N     P=0.767      P=0.539N     P=0.457N     | 
|COCH-ARM / FISHERS |                                                        |P=0.194N     P=0.709N     P=0.709N     P=0.314N     | 
|ORDER RESTRICTED   |                                                        |P=0.403N     (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.