National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/13624

TDMS Study 97013-99 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 11/05/03       
EXPERIMENT: 97013 TEST: 99                                                                                     TIME: 10:08:09       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-65406                              ROUTE: SKIN APPLICATION                                        NTP C#: 97013F       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
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                                                            FINAL#1 MICE                                                            
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 11/05/03       
EXPERIMENT: 97013 TEST: 99                                                                                     TIME: 10:08:09       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-65406                              ROUTE: SKIN APPLICATION                                        NTP C#: 97013F       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF     WATER DISINFECTION MODEL (BROMODICHLOR                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Kidney                                 Casts Protein                                                                                
                                       Nephropathy                                                                                  
Lymph Node, Mandibular                 Infiltration Cellular Plasma Cell                                                            
Stomach, Forestomach: Epithelium       Hyperplasia                                                                                  
Thyroid Gland                          Cyst                                                                                         
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Liver                                  Hematopoietic Cell Proliferation                                                             
Thymus                                 Atrophy                                                                                      
===============================================================                                                                     
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMO
DICHLOR                                                                                                                             
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/10 (50%)   3/10 (30%)   4/10 (40%)   4/10 (40%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     5/9.02       3/8.19       4/9.85       4/9.08      |0/5.97       0/4.87       0/8.76       0/5.96       | 
|POLY-3 PERCENT (g) |     55.5%        36.7%        40.6%        44.1%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     3/6 (50%)    3/8 (38%)    4/9 (44%)    4/8 (50%)   |0/5 (0%)     0/4 (0%)     0/7 (0%)     0/5 (0%)     | 
|FIRST INCIDENCE    |     153          274 (T)      274 (T)      274 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.345N     P=0.230N     P=0.266N     P=0.329N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.458N     P=0.386N     P=0.429N     P=0.494N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.468N     P=0.385N     P=0.459N     P=0.502N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.449N     P=0.359N     P=0.394N     P=0.477N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.433N     P=0.323N     P=0.619N     P=0.495N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.325N     P=0.500N     P=0.500N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.425N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    1/10 (10%)   1/10 (10%)  |7/10 (70%)   5/10 (50%)   5/10 (50%)   7/10 (70%)   | 
|POLY-3 RATE (b)    |     0/7.65       0/8.19       1/9.85       1/9.08      |7/8.09       5/7.42       5/9.58       7/7.55       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         10.2%        11.0%       |86.5%        67.4%        52.2%        92.8%        | 
|TERMINAL (d)       |     0/6 (0%)     0/8 (0%)     1/9 (11%)    1/8 (13%)   |4/5 (80%)    2/4 (50%)    3/7 (43%)    5/5 (100%)   | 
|FIRST INCIDENCE    |     ---          ---          274 (T)      274 (T)     |51           83           226          133          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.264      (e)          P=0.581      P=0.557     |P=0.549N     P=0.497N     P=0.160N     P=0.637N     | 
|POLY 3             |     P=0.281      (e)          P=0.550      P=0.534     |P=0.500      P=0.384N     P=0.145N     P=0.676      | 
|POLY 1.5           |     P=0.265      (e)          P=0.530      P=0.520     |P=0.494      P=0.344N     P=0.168N     P=0.684      | 
|POLY 6             |     P=0.296      (e)          P=0.570      P=0.551     |P=0.475      P=0.428N     P=0.153N     P=0.616      | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.581      P=0.557     |P=0.543      P=0.341N     P=0.260N     P=0.669N     | 
|COCH-ARM / FISHERS |     P=0.231      (e)          P=0.500      P=0.500     |P=0.500      P=0.325N     P=0.325N     P=0.686N     | 
|ORDER RESTRICTED   |     P=0.287      (e)          (e)          (e)         |P=0.191      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Casts Protein                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   2/10 (20%)   4/10 (40%)   2/10 (20%)  |2/10 (20%)   1/10 (10%)   1/10 (10%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |     1/8.47       2/8.19       4/10.00      2/10.00     |2/6.17       1/5.84       1/8.76       1/6.47       | 
|POLY-3 PERCENT (g) |     11.8%        24.4%        40.0%        20.0%       |32.4%        17.1%        11.4%        15.5%        | 
|TERMINAL (d)       |     0/6 (0%)     2/8 (25%)    3/9 (33%)    0/8 (0%)    |1/5 (20%)    0/4 (0%)     1/7 (14%)    0/5 (0%)     | 
|FIRST INCIDENCE    |     153          274 (T)      260          166         |254          83           274 (T)      217          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.487      P=0.542      P=0.292      P=0.558     |P=0.385N     P=0.560N     P=0.403N     P=0.521N     | 
|POLY 3             |     P=0.507      P=0.487      P=0.203      P=0.559     |P=0.367N     P=0.522N     P=0.373N     P=0.482N     | 
|POLY 1.5           |     P=0.457      P=0.479      P=0.178      P=0.534     |P=0.376N     P=0.498N     P=0.386N     P=0.480N     | 
|POLY 6             |     P=0.563      P=0.513      P=0.239      P=0.590     |P=0.366N     P=0.552N     P=0.393N     P=0.494N     | 
|LOGISTIC REGRESSION|     P=0.317      P=0.506      P=0.047 *    P=0.217     |P=0.396N     P=0.508N     P=0.363N     P=0.497N     | 
|COCH-ARM / FISHERS |     P=0.374      P=0.500      P=0.152      P=0.500     |P=0.404N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.297      (e)          (e)          (e)         |P=0.324N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   1/10 (10%)   2/10 (20%)   2/10 (20%)  |1/10 (10%)   0/10 (0%)    0/10 (0%)    2/10 (20%)   | 
|POLY-3 RATE (b)    |     1/7.65       1/8.19       2/9.85       2/9.22      |1/5.97       0/4.87       0/8.76       2/6.47       | 
|POLY-3 PERCENT (g) |     13.1%        12.2%        20.3%        21.7%       |16.8%        0.0%         0.0%         30.9%        | 
|TERMINAL (d)       |     1/6 (17%)    1/8 (13%)    2/9 (22%)    1/8 (13%)   |1/5 (20%)    0/4 (0%)     0/7 (0%)     1/5 (20%)    | 
|FIRST INCIDENCE    |     274 (T)      274 (T)      274 (T)      260         |274 (T)      ---          ---          217          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.415      P=0.702N     P=0.649      P=0.615     |P=0.264      P=0.545N     P=0.433N     P=0.500      | 
|POLY 3             |     P=0.411      P=0.749N     P=0.590      P=0.568     |P=0.276      P=0.541N     P=0.424N     P=0.531      | 
|POLY 1.5           |     P=0.382      P=0.762N     P=0.555      P=0.539     |P=0.264      P=0.522N     P=0.434N     P=0.526      | 
|POLY 6             |     P=0.440      P=0.726N     P=0.626      P=0.603     |P=0.282      P=0.557N     P=0.430N     P=0.530      | 
|LOGISTIC REGRESSION|     P=0.410      P=0.702N     P=0.649      P=0.594     |P=0.248      (e)          (e)          P=0.500      | 
|COCH-ARM / FISHERS |     P=0.327      P=0.763N     P=0.500      P=0.500     |P=0.239      P=0.500N     P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.509      (e)          (e)          (e)         |P=0.122      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Hydronephrosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    2/10 (20%)   0/10 (0%)    0/10 (0%)   |1/10 (10%)   1/10 (10%)   0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/7.65       2/8.19       0/9.85       0/9.08      |1/5.97       1/5.53       0/8.76       0/5.96       | 
|POLY-3 PERCENT (g) |     0.0%         24.4%        0.0%         0.0%        |16.8%        18.1%        0.0%         0.0%         | 
|TERMINAL (d)       |     0/6 (0%)     2/8 (25%)    0/9 (0%)     0/8 (0%)    |1/5 (20%)    0/4 (0%)     0/7 (0%)     0/5 (0%)     | 
|FIRST INCIDENCE    |     ---          274 (T)      ---          ---         |274 (T)      190          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.355N     P=0.298      (e)          (e)         |P=0.211N     P=0.736      P=0.433N     P=0.500N     | 
|POLY 3             |     P=0.352N     P=0.239      (e)          (e)         |P=0.210N     P=0.754      P=0.424N     P=0.500N     | 
|POLY 1.5           |     P=0.375N     P=0.225      (e)          (e)         |P=0.215N     P=0.760      P=0.434N     P=0.494N     | 
|POLY 6             |     P=0.323N     P=0.264      (e)          (e)         |P=0.208N     P=0.750      P=0.430N     P=0.511N     | 
|LOGISTIC REGRESSION|     (e)          P=0.298      (e)          (e)         |P=0.218N     P=0.754      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.403N     P=0.237      (e)          (e)         |P=0.231N     P=0.763N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.206N     (e)          (e)          (e)         |P=0.226N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/10 (60%)   5/10 (50%)   3/10 (30%)   6/10 (60%)  |2/10 (20%)   1/10 (10%)   4/10 (40%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |     6/8.25       5/8.19       3/9.85       6/9.08      |2/6.96       1/5.50       4/9.15       1/6.66       | 
|POLY-3 PERCENT (g) |     72.8%        61.1%        30.4%        66.1%       |28.7%        18.2%        43.7%        15.0%        | 
|TERMINAL (d)       |     5/6 (83%)    5/8 (63%)    3/9 (33%)    6/8 (75%)   |1/5 (20%)    0/4 (0%)     3/7 (43%)    0/5 (0%)     | 
|FIRST INCIDENCE    |     202          274 (T)      274 (T)      274 (T)     |51           196          233          184          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.376N     P=0.247N     P=0.048N*    P=0.380N    |P=0.464N     P=0.547N     P=0.465      P=0.494N     | 
|POLY 3             |     P=0.492N     P=0.509N     P=0.082N     P=0.589N    |P=0.468N     P=0.588N     P=0.463      P=0.517N     | 
|POLY 1.5           |     P=0.520N     P=0.538N     P=0.116N     P=0.627N    |P=0.478N     P=0.565N     P=0.436      P=0.514N     | 
|POLY 6             |     P=0.471N     P=0.437N     P=0.055N     P=0.534N    |P=0.473N     P=0.598N     P=0.457      P=0.522N     | 
|LOGISTIC REGRESSION|     P=0.384N     P=0.403N     P=0.070N     P=0.446N    |P=0.490N     P=0.490N     P=0.297      P=0.511N     | 
|COCH-ARM / FISHERS |     P=0.585      P=0.500N     P=0.185N     P=0.675N    |P=0.500N     P=0.500N     P=0.314      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.222N     (e)          (e)          (e)         |P=0.390N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Glomerulus                                                                                                               | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)   |1/10 (10%)   3/10 (30%)   0/10 (0%)    2/10 (20%)   | 
|POLY-3 RATE (b)    |     0/7.65       0/8.19       0/9.85       0/9.08      |1/6.92       3/7.13       0/8.76       2/7.35       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |14.4%        42.1%        0.0%         27.2%        | 
|TERMINAL (d)       |     0/6 (0%)     0/8 (0%)     0/9 (0%)     0/8 (0%)    |0/5 (0%)     0/4 (0%)     0/7 (0%)     0/5 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |98           94           ---          133          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.612      P=0.281      P=0.455N     P=0.547      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.601      P=0.291      P=0.453N     P=0.522      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.595      P=0.289      P=0.456N     P=0.517      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.600      P=0.301      P=0.462N     P=0.525      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.493      P=0.301      P=0.993N     P=0.480      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.559      P=0.291      P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.358N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/10 (30%)   1/10 (10%)   1/10 (10%)   1/10 (10%)  |4/10 (40%)   2/10 (20%)   1/10 (10%)   4/10 (40%)   | 
|POLY-3 RATE (b)    |     3/8.47       1/8.19       1/9.85       1/9.08      |4/6.17       2/4.87       1/8.76       4/6.96       | 
|POLY-3 PERCENT (g) |     35.4%        12.2%        10.2%        11.0%       |64.8%        41.1%        11.4%        57.5%        | 
|TERMINAL (d)       |     2/6 (33%)    1/8 (13%)    1/9 (11%)    1/8 (13%)   |3/5 (60%)    2/4 (50%)    1/7 (14%)    3/5 (60%)    | 
|FIRST INCIDENCE    |     153          274 (T)      274 (T)      274 (T)     |254          274 (T)      274 (T)      37           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.173N     P=0.240N     P=0.195N     P=0.222N    |P=0.577      P=0.447N     P=0.080N     P=0.663      | 
|POLY 3             |     P=0.205N     P=0.299N     P=0.232N     P=0.260N    |P=0.580N     P=0.431N     P=0.044N*    P=0.615N     | 
|POLY 1.5           |     P=0.211N     P=0.310N     P=0.256N     P=0.276N    |P=0.590N     P=0.358N     P=0.054N     P=0.592N     | 
|POLY 6             |     P=0.202N     P=0.270N     P=0.204N     P=0.237N    |P=0.586N     P=0.507N     P=0.051N     P=0.673N     | 
|LOGISTIC REGRESSION|     P=0.228N     P=0.288N     P=0.441N     P=0.325N    |P=0.582      P=0.474N     P=0.054N     P=0.674N     | 
|COCH-ARM / FISHERS |     P=0.227N     P=0.291N     P=0.291N     P=0.291N    |P=0.524      P=0.314N     P=0.152N     P=0.675N     | 
|ORDER RESTRICTED   |     P=0.135N     (e)          (e)          (e)         |P=0.155N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/10 (60%)   3/10 (30%)   6/10 (60%)   3/10 (30%)  |7/10 (70%)   6/10 (60%)   9/10 (90%)   5/10 (50%)   | 
|POLY-3 RATE (b)    |     6/8.86       3/9.15       6/10.00      3/9.22      |7/7.17       6/6.77       9/9.56       5/6.66       | 
|POLY-3 PERCENT (g) |     67.7%        32.8%        60.0%        32.5%       |97.7%        88.7%        94.1%        75.1%        | 
|TERMINAL (d)       |     4/6 (67%)    2/8 (25%)    5/9 (56%)    2/8 (25%)   |5/5 (100%)   4/4 (100%)   7/7 (100%)   4/5 (80%)    | 
|FIRST INCIDENCE    |     153          91           260          260         |51           96           229          184          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.137N     P=0.137N     P=0.317N     P=0.107N    |P=0.189N     P=0.645      P=0.615N     P=0.320N     | 
|POLY 3             |     P=0.195N     P=0.150N     P=0.551N     P=0.146N    |P=0.150N     P=0.754N     P=0.879N     P=0.302N     | 
|POLY 1.5           |     P=0.207N     P=0.168N     P=0.602N     P=0.164N    |P=0.217N     P=0.550N     P=0.835      P=0.298N     | 
|POLY 6             |     P=0.181N     P=0.125N     P=0.488N     P=0.123N    |P=0.132N     P=1.000N     P=0.987N     P=0.373N     | 
|LOGISTIC REGRESSION|     P=0.238N     P=0.180N     P=0.669N     P=0.168N    |P=0.135N     P=0.574N     P=0.692N     P=0.225N     | 
|COCH-ARM / FISHERS |     P=0.226N     P=0.185N     P=0.675N     P=0.185N    |P=0.304N     P=0.500N     P=0.291      P=0.325N     | 
|ORDER RESTRICTED   |     P=0.104N     (e)          (e)          (e)         |P=0.074N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/10 (60%)   7/10 (70%)   8/10 (80%)   7/10 (70%)  |4/10 (40%)   4/10 (40%)   7/10 (70%)   6/10 (60%)   | 
|POLY-3 RATE (b)    |     6/8.58       7/8.19       8/10.00      7/9.08      |4/5.97       4/4.87       7/9.58       6/6.66       | 
|POLY-3 PERCENT (g) |     70.0%        85.5%        80.0%        77.1%       |67.0%        82.2%        73.0%        90.1%        | 
|TERMINAL (d)       |     4/6 (67%)    7/8 (88%)    7/9 (78%)    7/8 (88%)   |4/5 (80%)    4/4 (100%)   5/7 (71%)    5/5 (100%)   | 
|FIRST INCIDENCE    |     211          274 (T)      260          274 (T)     |274 (T)      274 (T)      226          184          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.458N     P=0.568N     P=0.543N     P=0.546N    |P=0.182      P=0.545      P=0.479      P=0.257      | 
|POLY 3             |     P=0.545      P=0.428      P=0.516      P=0.580     |P=0.280      P=0.556      P=0.618      P=0.364      | 
|POLY 1.5           |     P=0.505      P=0.422      P=0.438      P=0.550     |P=0.249      P=0.642      P=0.514      P=0.359      | 
|POLY 6             |     P=0.562      P=0.467      P=0.583      P=0.601     |P=0.272      P=0.457      P=0.656      P=0.337      | 
|LOGISTIC REGRESSION|     P=0.516N     P=0.571      P=0.585      P=0.692N    |P=0.150      P=0.545      P=0.533      P=0.236      | 
|COCH-ARM / FISHERS |     P=0.408      P=0.500      P=0.314      P=0.500     |P=0.181      P=0.675N     P=0.185      P=0.328      | 
|ORDER RESTRICTED   |     P=0.465      (e)          (e)          (e)         |P=0.243      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)   |0/10 (0%)    0/10 (0%)    2/10 (20%)   0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/7.65       0/8.19       1/9.85       0/9.08      |0/5.97       0/4.87       2/9.58       0/5.96       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         10.2%        0.0%        |0.0%         0.0%         20.9%        0.0%         | 
|TERMINAL (d)       |     0/6 (0%)     0/8 (0%)     1/9 (11%)    0/8 (0%)    |0/5 (0%)     0/4 (0%)     0/7 (0%)     0/5 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          274 (T)      ---         |---          ---          226          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.729      (e)          P=0.581      (e)         |P=0.600      (e)          P=0.331      (e)          | 
|POLY 3             |     P=0.749      (e)          P=0.550      (e)         |P=0.610      (e)          P=0.349      (e)          | 
|POLY 1.5           |     P=0.729      (e)          P=0.530      (e)         |P=0.617      (e)          P=0.323      (e)          | 
|POLY 6             |     P=0.769      (e)          P=0.570      (e)         |P=0.585      (e)          P=0.357      (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.581      (e)         |P=0.608      (e)          P=0.204      (e)          | 
|COCH-ARM / FISHERS |     P=0.696      (e)          P=0.500      (e)         |P=0.597      (e)          P=0.237      (e)          | 
|ORDER RESTRICTED   |     P=0.425      (e)          (e)          (e)         |P=0.331      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    1/10 (10%)   1/10 (10%)   0/10 (0%)   |3/10 (30%)   0/10 (0%)    1/10 (10%)   1/9 (11%)    | 
|POLY-3 RATE (b)    |     0/7.65       1/8.19       1/10.00      0/9.08      |3/6.17       0/4.87       1/8.76       1/5.92       | 
|POLY-3 PERCENT (g) |     0.0%         12.2%        10.0%        0.0%        |48.6%        0.0%         11.4%        16.9%        | 
|TERMINAL (d)       |     0/6 (0%)     1/8 (13%)    0/9 (0%)     0/8 (0%)    |2/5 (40%)    0/4 (0%)     1/7 (14%)    1/5 (20%)    | 
|FIRST INCIDENCE    |     ---          274 (T)      260          ---         |254          ---          274 (T)      274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.537N     P=0.557      P=0.602      (e)         |P=0.257N     P=0.168N     P=0.196N     P=0.309N     | 
|POLY 3             |     P=0.545N     P=0.514      P=0.553      (e)         |P=0.232N     P=0.123N     P=0.159N     P=0.288N     | 
|POLY 1.5           |     P=0.566N     P=0.502      P=0.532      (e)         |P=0.253N     P=0.100N     P=0.172N     P=0.282N     | 
|POLY 6             |     P=0.521N     P=0.534      P=0.575      (e)         |P=0.224N     P=0.150N     P=0.173N     P=0.319N     | 
|LOGISTIC REGRESSION|     P=0.566N     P=0.557      P=0.510      (e)         |P=0.247N     P=0.134N     P=0.156N     P=0.289N     | 
|COCH-ARM / FISHERS |     P=0.597N     P=0.500      P=0.500      (e)         |P=0.315N     P=0.105N     P=0.291N     P=0.333N     | 
|ORDER RESTRICTED   |     P=0.412N     (e)          (e)          (e)         |P=0.071N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Infiltration Cellular Plasma Cell                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   0/10 (0%)    0/10 (0%)    0/10 (0%)   |0/10 (0%)    1/10 (10%)   0/10 (0%)    0/9 (0%)     | 
|POLY-3 RATE (b)    |     2/8.03       0/8.19       0/9.85       0/9.08      |0/5.97       1/4.87       0/8.76       0/5.92       | 
|POLY-3 PERCENT (g) |     24.9%        0.0%         0.0%         0.0%        |0.0%         20.6%        0.0%         0.0%         | 
|TERMINAL (d)       |     1/6 (17%)    0/8 (0%)     0/9 (0%)     0/8 (0%)    |0/5 (0%)     1/4 (25%)    0/7 (0%)     0/5 (0%)     | 
|FIRST INCIDENCE    |     233          ---          ---          ---         |---          274 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.088N     P=0.195N     P=0.161N     P=0.183N    |P=0.553N     P=0.455      (e)          (e)          | 
|POLY 3             |     P=0.101N     P=0.218N     P=0.179N     P=0.195N    |P=0.592N     P=0.458      (e)          (e)          | 
|POLY 1.5           |     P=0.098N     P=0.228N     P=0.195N     P=0.207N    |P=0.579N     P=0.478      (e)          (e)          | 
|POLY 6             |     P=0.107N     P=0.203N     P=0.165N     P=0.184N    |P=0.601N     P=0.442      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.108N     P=0.225N     P=0.230N     P=0.221N    |(e)          P=0.455      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.110N     P=0.237N     P=0.237N     P=0.237N    |P=0.585N     P=0.500      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.015N*    (e)          (e)          (e)         |P=0.341N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/10 (10%)   0/10 (0%)    3/10 (30%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |                                                        |1/5.97       0/4.87       3/8.76       1/5.96       | 
|POLY-3 PERCENT (g) |                                                        |16.8%        0.0%         34.3%        16.8%        | 
|TERMINAL (d)       |                                                        |1/5 (20%)    0/4 (0%)     3/7 (43%)    1/5 (20%)    | 
|FIRST INCIDENCE    |                                                        |274 (T)      ---          274 (T)      274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.507      P=0.545N     P=0.421      P=0.773      | 
|POLY 3             |                                                        |P=0.511      P=0.541N     P=0.446      P=0.770      | 
|POLY 1.5           |                                                        |P=0.507      P=0.522N     P=0.424      P=0.762N     | 
|POLY 6             |                                                        |P=0.493      P=0.557N     P=0.432      P=0.760      | 
|LOGISTIC REGRESSION|                                                        |P=0.507      (e)          P=0.421      P=0.773      | 
|COCH-ARM / FISHERS |                                                        |P=0.468      P=0.500N     P=0.291      P=0.763N     | 
|ORDER RESTRICTED   |                                                        |P=0.361      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/10 (10%)   1/10 (10%)   2/10 (20%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |                                                        |1/6.17       1/5.81       2/9.20       1/5.96       | 
|POLY-3 PERCENT (g) |                                                        |16.2%        17.2%        21.7%        16.8%        | 
|TERMINAL (d)       |                                                        |0/5 (0%)     0/4 (0%)     1/7 (14%)    1/5 (20%)    | 
|FIRST INCIDENCE    |                                                        |254          104          226          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.618      P=0.716      P=0.614      P=0.740      | 
|POLY 3             |                                                        |P=0.594      P=0.756      P=0.639      P=0.762      | 
|POLY 1.5           |                                                        |P=0.605      P=0.768      P=0.620      P=0.766N     | 
|POLY 6             |                                                        |P=0.566      P=0.739      P=0.631      P=0.744      | 
|LOGISTIC REGRESSION|                                                        |P=0.610      P=0.768N     P=0.596      P=0.775      | 
|COCH-ARM / FISHERS |                                                        |P=0.596      P=0.763N     P=0.500      P=0.763N     | 
|ORDER RESTRICTED   |                                                        |P=0.677      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   2/10 (20%)   1/10 (10%)   2/10 (20%)  |0/10 (0%)    1/10 (10%)   1/10 (10%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |     1/7.65       2/8.19       1/9.85       2/9.08      |0/5.97       1/5.84       1/8.76       1/5.96       | 
|POLY-3 PERCENT (g) |     13.1%        24.4%        10.2%        22.0%       |0.0%         17.1%        11.4%        16.8%        | 
|TERMINAL (d)       |     1/6 (17%)    2/8 (25%)    1/9 (11%)    2/8 (25%)   |0/5 (0%)     0/4 (0%)     1/7 (14%)    1/5 (20%)    | 
|FIRST INCIDENCE    |     274 (T)      274 (T)      274 (T)      274 (T)     |---          83           274 (T)      274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.528      P=0.607      P=0.673N     P=0.607     |P=0.396      P=0.521      P=0.567      P=0.500      | 
|POLY 3             |     P=0.516      P=0.525      P=0.702N     P=0.562     |P=0.388      P=0.495      P=0.574      P=0.500      | 
|POLY 1.5           |     P=0.489      P=0.503      P=0.726N     P=0.536     |P=0.396      P=0.505      P=0.564      P=0.506      | 
|POLY 6             |     P=0.542      P=0.562      P=0.675N     P=0.593     |P=0.369      P=0.485      P=0.569      P=0.489      | 
|LOGISTIC REGRESSION|     P=0.528      P=0.607      P=0.673N     P=0.607     |P=0.379      P=0.439      P=0.567      P=0.500      | 
|COCH-ARM / FISHERS |     P=0.441      P=0.500      P=0.763N     P=0.500     |P=0.380      P=0.500      P=0.500      P=0.500      | 
|ORDER RESTRICTED   |     P=0.511      (e)          (e)          (e)         |P=0.318      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    1/10 (10%)   0/10 (0%)    1/10 (10%)  |0/10 (0%)    0/10 (0%)    2/10 (20%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/7.65       1/8.19       0/9.85       1/9.08      |0/5.97       0/4.87       2/8.76       1/5.96       | 
|POLY-3 PERCENT (g) |     0.0%         12.2%        0.0%         11.0%       |0.0%         0.0%         22.8%        16.8%        | 
|TERMINAL (d)       |     0/6 (0%)     1/8 (13%)    0/9 (0%)     1/8 (13%)   |0/5 (0%)     0/4 (0%)     2/7 (29%)    1/5 (20%)    | 
|FIRST INCIDENCE    |     ---          274 (T)      ---          274 (T)     |---          ---          274 (T)      274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.448      P=0.557      (e)          P=0.557     |P=0.253      (e)          P=0.308      P=0.500      | 
|POLY 3             |     P=0.455      P=0.514      (e)          P=0.534     |P=0.256      (e)          P=0.322      P=0.500      | 
|POLY 1.5           |     P=0.434      P=0.502      (e)          P=0.520     |P=0.258      (e)          P=0.309      P=0.506      | 
|POLY 6             |     P=0.479      P=0.534      (e)          P=0.551     |P=0.240      (e)          P=0.313      P=0.489      | 
|LOGISTIC REGRESSION|     (e)          P=0.557      (e)          P=0.557     |(e)          (e)          P=0.308      P=0.500      | 
|COCH-ARM / FISHERS |     P=0.403      P=0.500      (e)          P=0.500     |P=0.239      (e)          P=0.237      P=0.500      | 
|ORDER RESTRICTED   |     P=0.285      (e)          (e)          (e)         |P=0.235      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Inflammation Focal                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   2/10 (20%)   1/10 (10%)   0/10 (0%)   |2/10 (20%)   1/10 (10%)   0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     1/7.65       2/8.19       1/9.85       0/9.08      |2/5.97       1/4.87       0/8.76       1/6.47       | 
|POLY-3 PERCENT (g) |     13.1%        24.4%        10.2%        0.0%        |33.5%        20.6%        0.0%         15.5%        | 
|TERMINAL (d)       |     1/6 (17%)    2/8 (25%)    1/9 (11%)    0/8 (0%)    |2/5 (40%)    1/4 (25%)    0/7 (0%)     0/5 (0%)     | 
|FIRST INCIDENCE    |     274 (T)      274 (T)      274 (T)      ---         |274 (T)      274 (T)      ---          217          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.180N     P=0.607      P=0.673N     P=0.443N    |P=0.321N     P=0.588N     P=0.158N     P=0.500N     | 
|POLY 3             |     P=0.197N     P=0.525      P=0.702N     P=0.466N    |P=0.318N     P=0.579N     P=0.141N     P=0.469N     | 
|POLY 1.5           |     P=0.214N     P=0.503      P=0.726N     P=0.480N    |P=0.325N     P=0.542N     P=0.152N     P=0.473N     | 
|POLY 6             |     P=0.180N     P=0.562      P=0.675N     P=0.448N    |P=0.315N     P=0.610N     P=0.144N     P=0.470N     | 
|LOGISTIC REGRESSION|     P=0.180N     P=0.607      P=0.673N     (e)         |P=0.325N     P=0.588N     (e)          P=0.500N     | 
|COCH-ARM / FISHERS |     P=0.238N     P=0.500      P=0.763N     P=0.500N    |P=0.361N     P=0.500N     P=0.237N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.192N     (e)          (e)          (e)         |P=0.153N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin: Control Epidermis                                                                                                          | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%)  |2/10 (20%)   0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/7.65       0/8.19       0/9.85       1/9.08      |2/5.97       0/4.87       0/8.76       1/5.96       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         11.0%       |33.5%        0.0%         0.0%         16.8%        | 
|TERMINAL (d)       |     0/6 (0%)     0/8 (0%)     0/9 (0%)     1/8 (13%)   |2/5 (40%)    0/4 (0%)     0/7 (0%)     1/5 (20%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          274 (T)     |274 (T)      ---          ---          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.215      (e)          (e)          P=0.557     |P=0.428N     P=0.277N     P=0.158N     P=0.500N     | 
|POLY 3             |     P=0.220      (e)          (e)          P=0.534     |P=0.396N     P=0.265N     P=0.141N     P=0.500N     | 
|POLY 1.5           |     P=0.213      (e)          (e)          P=0.520     |P=0.417N     P=0.242N     P=0.152N     P=0.489N     | 
|POLY 6             |     P=0.226      (e)          (e)          P=0.551     |P=0.380N     P=0.286N     P=0.144N     P=0.521N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.557     |P=0.428N     (e)          (e)          P=0.500N     | 
|COCH-ARM / FISHERS |     P=0.196      (e)          (e)          P=0.500     |P=0.460N     P=0.237N     P=0.237N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.151      (e)          (e)          (e)         |P=0.101N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/10 (40%)   2/10 (20%)   3/10 (30%)   1/10 (10%)  |3/10 (30%)   2/10 (20%)   1/10 (10%)   2/10 (20%)   | 
|POLY-3 RATE (b)    |     4/8.47       2/8.19       3/10.00      1/9.08      |3/6.17       2/4.87       1/8.76       2/5.96       | 
|POLY-3 PERCENT (g) |     47.2%        24.4%        30.0%        11.0%       |48.6%        41.1%        11.4%        33.5%        | 
|TERMINAL (d)       |     3/6 (50%)    2/8 (25%)    2/9 (22%)    1/8 (13%)   |2/5 (40%)    2/4 (50%)    1/7 (14%)    2/5 (40%)    | 
|FIRST INCIDENCE    |     153          274 (T)      260          274 (T)     |254          274 (T)      274 (T)      274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.083N     P=0.222N     P=0.295N     P=0.100N    |P=0.345N     P=0.636N     P=0.196N     P=0.519N     | 
|POLY 3             |     P=0.104N     P=0.326N     P=0.394N     P=0.117N    |P=0.329N     P=0.636N     P=0.159N     P=0.520N     | 
|POLY 1.5           |     P=0.114N     P=0.342N     P=0.439N     P=0.131N    |P=0.340N     P=0.570N     P=0.172N     P=0.494N     | 
|POLY 6             |     P=0.096N     P=0.285N     P=0.337N     P=0.098N    |P=0.336N     P=0.693N     P=0.173N     P=0.566N     | 
|LOGISTIC REGRESSION|     P=0.112N     P=0.308N     P=0.574N     P=0.156N    |P=0.349N     P=0.675N     P=0.156N     P=0.534N     | 
|COCH-ARM / FISHERS |     P=0.133N     P=0.314N     P=0.500N     P=0.152N    |P=0.395N     P=0.500N     P=0.291N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.073N     (e)          (e)          (e)         |P=0.236N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   0/10 (0%)    0/10 (0%)    0/10 (0%)   |1/10 (10%)   0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     2/8.25       0/8.19       0/9.85       0/9.08      |1/5.97       0/4.87       0/8.76       1/5.96       | 
|POLY-3 PERCENT (g) |     24.3%        0.0%         0.0%         0.0%        |16.8%        0.0%         0.0%         16.8%        | 
|TERMINAL (d)       |     1/6 (17%)    0/8 (0%)     0/9 (0%)     0/8 (0%)    |1/5 (20%)    0/4 (0%)     0/7 (0%)     1/5 (20%)    | 
|FIRST INCIDENCE    |     202          ---          ---          ---         |274 (T)      ---          ---          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.099N     P=0.220N     P=0.185N     P=0.208N    |P=0.623      P=0.545N     P=0.433N     P=0.773      | 
|POLY 3             |     P=0.098N     P=0.224N     P=0.184N     P=0.201N    |P=0.634      P=0.541N     P=0.424N     P=0.770      | 
|POLY 1.5           |     P=0.097N     P=0.232N     P=0.199N     P=0.211N    |P=0.624      P=0.522N     P=0.434N     P=0.762N     | 
|POLY 6             |     P=0.103N     P=0.210N     P=0.170N     P=0.190N    |P=0.636      P=0.557N     P=0.430N     P=0.760      | 
|LOGISTIC REGRESSION|     P=0.123N     P=0.226N     P=0.329N     P=0.259N    |P=0.623      (e)          (e)          P=0.773      | 
|COCH-ARM / FISHERS |     P=0.110N     P=0.237N     P=0.237N     P=0.237N    |P=0.597      P=0.500N     P=0.500N     P=0.763N     | 
|ORDER RESTRICTED   |     P=0.016N*    (e)          (e)          (e)         |P=0.377      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   2/10 (20%)   0/10 (0%)    1/10 (10%)  |                                                    | 
|POLY-3 RATE (b)    |     1/7.65       2/8.19       0/9.85       1/9.08      |                                                    | 
|POLY-3 PERCENT (g) |     13.1%        24.4%        0.0%         11.0%       |                                                    | 
|TERMINAL (d)       |     1/6 (17%)    2/8 (25%)    0/9 (0%)     1/8 (13%)   |                                                    | 
|FIRST INCIDENCE    |     274 (T)      274 (T)      ---          274 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.429N     P=0.607      P=0.419N     P=0.702N    |                                                    | 
|POLY 3             |     P=0.460N     P=0.525      P=0.450N     P=0.724N    |                                                    | 
|POLY 1.5           |     P=0.475N     P=0.503      P=0.469N     P=0.740N    |                                                    | 
|POLY 6             |     P=0.446N     P=0.562      P=0.429N     P=0.703N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.429N     P=0.607      (e)          P=0.702N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.500      P=0.500N     P=0.763N    |                                                    | 
|ORDER RESTRICTED   |     P=0.318N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/9 (11%)    0/10 (0%)    2/9 (22%)    1/9 (11%)   |2/10 (20%)   6/10 (60%)   2/10 (20%)   2/10 (20%)   | 
|POLY-3 RATE (b)    |     1/7.25       0/8.19       2/9.00       1/8.85      |2/7.92       6/10.00      2/9.62       2/7.35       | 
|POLY-3 PERCENT (g) |     13.8%        0.0%         22.2%        11.3%       |25.3%        60.0%        20.8%        27.2%        | 
|TERMINAL (d)       |     0/5 (0%)     0/8 (0%)     2/9 (22%)    0/7 (0%)    |0/5 (0%)     0/4 (0%)     0/7 (0%)     0/5 (0%)     | 
|FIRST INCIDENCE    |     202          ---          274 (T)      166         |51           83           226          133          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.547      P=0.523N     P=0.648      P=0.749N    |P=0.303N     P=0.131      P=0.588N     P=0.665N     | 
|POLY 3             |     P=0.579      P=0.475N     P=0.578      P=0.715N    |P=0.332N     P=0.162      P=0.630N     P=0.682      | 
|POLY 1.5           |     P=0.552      P=0.483N     P=0.548      P=0.733N    |P=0.334N     P=0.136      P=0.645N     P=0.683      | 
|POLY 6             |     P=0.597      P=0.461N     P=0.609      P=0.697N    |P=0.333N     P=0.179      P=0.626N     P=0.682      | 
|LOGISTIC REGRESSION|     P=0.400      P=0.451N     P=0.406      P=0.672     |P=0.442N     P=0.040 *    P=0.194      P=0.695      | 
|COCH-ARM / FISHERS |     P=0.488      P=0.474N     P=0.500      P=0.765N    |P=0.320N     P=0.085      P=0.709N     P=0.709N     | 
|ORDER RESTRICTED   |     P=0.432      (e)          (e)          (e)         |P=0.326N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/9 (44%)    2/10 (20%)   1/9 (11%)    3/9 (33%)   |3/10 (30%)   2/10 (20%)   2/10 (20%)   3/10 (30%)   | 
|POLY-3 RATE (b)    |     4/7.63       2/8.19       1/9.00       3/8.22      |3/5.97       2/5.82       2/9.15       3/5.96       | 
|POLY-3 PERCENT (g) |     52.4%        24.4%        11.1%        36.5%       |50.3%        34.4%        21.9%        50.3%        | 
|TERMINAL (d)       |     2/5 (40%)    2/8 (25%)    1/9 (11%)    2/7 (29%)   |3/5 (60%)    1/4 (25%)    1/7 (14%)    3/5 (60%)    | 
|FIRST INCIDENCE    |     202          274 (T)      274 (T)      260         |274 (T)      96           233          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.346N     P=0.190N     P=0.068N     P=0.340N    |P=0.602      P=0.607N     P=0.339N     P=0.730      | 
|POLY 3             |     P=0.422N     P=0.267N     P=0.088N     P=0.449N    |P=0.598      P=0.514N     P=0.288N     P=0.716      | 
|POLY 1.5           |     P=0.433N     P=0.276N     P=0.105N     P=0.469N    |P=0.590      P=0.491N     P=0.323N     P=0.692N     | 
|POLY 6             |     P=0.417N     P=0.248N     P=0.075N     P=0.427N    |P=0.591      P=0.543N     P=0.285N     P=0.691      | 
|LOGISTIC REGRESSION|     P=0.422N     P=0.240N     P=0.167N     P=0.453N    |P=0.604N     P=0.561N     P=0.309N     P=0.730      | 
|COCH-ARM / FISHERS |     P=0.470N     P=0.259N     P=0.147N     P=0.500N    |P=0.549      P=0.500N     P=0.500N     P=0.686N     | 
|ORDER RESTRICTED   |     P=0.167N     (e)          (e)          (e)         |P=0.446N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 97013 TEST: 99                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -      WATER DISINFECTION MODEL (BROMOD
ICHLOR                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    3/10 (30%)  |2/10 (20%)   3/10 (30%)   1/10 (10%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/7.65       0/8.19       0/9.85       3/9.08      |2/6.93       3/5.53       1/9.15       1/5.96       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         33.1%       |28.9%        54.2%        10.9%        16.8%        | 
|TERMINAL (d)       |     0/6 (0%)     0/8 (0%)     0/9 (0%)     3/8 (38%)   |1/5 (20%)    2/4 (50%)    0/7 (0%)     1/5 (20%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          274 (T)     |96           190          233          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.012 *    (e)          (e)          P=0.159     |P=0.241N     P=0.424      P=0.416N     P=0.500N     | 
|POLY 3             |     P=0.007 **   (e)          (e)          P=0.125     |P=0.253N     P=0.375      P=0.399N     P=0.557N     | 
|POLY 1.5           |     P=0.006 **   (e)          (e)          P=0.111     |P=0.251N     P=0.417      P=0.412N     P=0.532N     | 
|POLY 6             |     P=0.007 **   (e)          (e)          P=0.144     |P=0.262N     P=0.357      P=0.403N     P=0.581N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.159     |P=0.242N     P=0.467      P=0.655N     P=0.497N     | 
|COCH-ARM / FISHERS |     P=0.010 *    (e)          (e)          P=0.105     |P=0.263N     P=0.500      P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.007 **   (e)          (e)          (e)         |P=0.224N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      64 MG/KG     128          256         |0 MG/KG      64 MG/KG     128          256          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |5/10 (50%)   4/10 (40%)   5/10 (50%)   7/10 (70%)   | 
|POLY-3 RATE (b)    |                                                        |5/5.97       4/4.87       5/8.76       7/7.16       | 
|POLY-3 PERCENT (g) |                                                        |83.8%        82.2%        57.1%        97.7%        | 
|TERMINAL (d)       |                                                        |5/5 (100%)   4/4 (100%)   5/7 (71%)    5/5 (100%)   | 
|FIRST INCIDENCE    |                                                        |274 (T)      274 (T)      274 (T)      184          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.150      P=1.000N     P=0.308N     P=0.257      | 
|POLY 3             |                                                        |P=0.319      P=0.822N     P=0.301N     P=0.544      | 
|POLY 1.5           |                                                        |P=0.258      P=0.639N     P=0.367N     P=0.420      | 
|POLY 6             |                                                        |P=0.386      P=0.854      P=0.313N     P=0.679      | 
|LOGISTIC REGRESSION|                                                        |P=0.124      P=1.000N     P=0.308N     P=0.244      | 
|COCH-ARM / FISHERS |                                                        |P=0.181      P=0.500N     P=0.672N     P=0.325      | 
|ORDER RESTRICTED   |                                                        |P=0.136      (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.