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TR 393 Mouse Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                       SODIUM FLUORIDE                                   DATE: 09/17/94       
EXPERIMENT: 05131 TEST: 02                                                                                     TIME: 08:50:39       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-55102          ROUTE: DOSED WATER                                                                 NTP C#: 55221B       
PATHOLOGIST: J. TOFT                         S. EUSTIS                                                         CAS: 7681-49-4       
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Battelle Columbus                                       SODIUM FLUORIDE                                   DATE: 09/17/94      
EXPERIMENT: 05131 TEST: 02                                                                                     TIME: 08:50:39      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-55102          ROUTE: DOSED WATER                                                                 NTP C#: 55221B      
PATHOLOGIST: J. TOFT                         S. EUSTIS                                                         CAS: 7681-49-4      
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                       SODIUM FLUORIDE                                   DATE: 09/17/94       
EXPERIMENT: 05131 TEST: 02                                                                                     TIME: 08:50:39       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-55102          ROUTE: DOSED WATER                                                                 NTP C#: 55221B       
PATHOLOGIST: J. TOFT                         S. EUSTIS                                                         CAS: 7681-49-4       
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                        IN THE ANALYSIS OF THE STUDY OF SODIUM FLUORIDE
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Harderian Gland               Adenoma
                                                           Carcinoma or Adenoma
                             Liver                         Hepatoblastoma
                                                           Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatoblastoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Carcinoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             All Organs                    Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Harderian Gland               Adenoma
                             Liver                         Hepatoblastoma
                                                           Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                             All Organs                    Hemangiosarcoma or Hemangioma
                                                           Malignant Lymphoma And Histiocytic Sarcoma
                                                           Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,
                                                            NOS, or Undifferentiated Cell Type
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   1
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/131 (8%)   8/60 (13%)   6/62 (10%)   6/100 (6%) |  0/141 (0%)   0/62 (0%)    0/63 (0%)    0/99 (0%)  |
|ADJUSTED (b)           |  16.3%        19.9%        16.2%         9.2%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  8/58 (14%)   7/39 (18%)   6/37 (16%)   6/65 (9%)  |  0/53 (0%)    0/38 (0%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   669          707          729 (T)      729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.083N     P=0.436      P=0.571N     P=0.157N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.126N     P=0.335      P=0.561      P=0.227N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.115N     P=0.357      P=0.564      P=0.214N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.255N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.162      P=0.410      P=0.416N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/128 (0%)   1/60 (2%)    0/62 (0%)    1/99 (1%)  |  0/138 (0%)   2/62 (3%)    1/63 (2%)    1/98 (1%)  |
|ADJUSTED (b)           |   0.0%         2.6%         0.0%         1.5%      |   0.0%         5.3%         2.9%         2.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/56 (0%)    1/39 (3%)    0/37 (0%)    1/65 (2%)  |  0/51 (0%)    2/38 (5%)    1/34 (3%)    1/51 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          729 (T)   |   ---          729 (T)      729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.502      P=0.428        (e)        P=0.530    |  P=0.549      P=0.176      P=0.419      P=0.500    |
|INCIDENTAL TUMOR       |  P=0.502      P=0.428        (e)        P=0.530    |  P=0.549      P=0.176      P=0.419      P=0.500    |
|LOGISTIC REGRESSION    |  P=0.502      P=0.428        (e)        P=0.530    |  P=0.549      P=0.176      P=0.419      P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.427                                           |  P=0.471                                           |
|FISHER EXACT           |               P=0.319        (e)        P=0.436    |               P=0.095      P=0.313      P=0.415    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   2
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/128 (0%)   2/60 (3%)    0/62 (0%)    1/99 (1%)  |  0/138 (0%)   2/62 (3%)    1/63 (2%)    1/98 (1%)  |
|ADJUSTED (b)           |   0.0%         5.1%         0.0%         1.5%      |   0.0%         5.3%         2.9%         2.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/56 (0%)    2/39 (5%)    0/37 (0%)    1/65 (2%)  |  0/51 (0%)    2/38 (5%)    1/34 (3%)    1/51 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          729 (T)   |   ---          729 (T)      729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.556N     P=0.163        (e)        P=0.530    |  P=0.549      P=0.176      P=0.419      P=0.500    |
|INCIDENTAL TUMOR       |  P=0.556N     P=0.163        (e)        P=0.530    |  P=0.549      P=0.176      P=0.419      P=0.500    |
|LOGISTIC REGRESSION    |  P=0.556N     P=0.163        (e)        P=0.530    |  P=0.549      P=0.176      P=0.419      P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.586                                           |  P=0.471                                           |
|FISHER EXACT           |               P=0.101        (e)        P=0.436    |               P=0.095      P=0.313      P=0.415    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/131 (0%)   1/60 (2%)    0/62 (0%)    0/100 (0%) |  2/142 (1%)   0/62 (0%)    0/63 (0%)    0/99 (0%)  |
|ADJUSTED (b)           |   0.0%         1.7%         0.0%         0.0%      |   2.7%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    0/39 (0%)    0/37 (0%)    0/65 (0%)  |  1/53 (2%)    0/38 (0%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          458 (I)      ---          ---       |   420          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.432N     P=0.500        (e)          (e)      |  P=0.149N     P=0.357N     P=0.374N     P=0.282N   |
|INCIDENTAL TUMOR       |  P=0.432N     P=0.500        (e)          (e)      |  P=0.208N     P=0.451N     P=0.443N     P=0.402N   |
|LOGISTIC REGRESSION    |  P=0.453N     P=0.252        (e)          (e)      |  P=0.167N     P=0.444N     P=0.435N     P=0.322N   |
|COCHRAN-ARMITAGE       |  P=0.452N                                          |  P=0.167N                                          |
|FISHER EXACT           |               P=0.314        (e)          (e)      |               P=0.483N     P=0.479N     P=0.346N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   3
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/131 (0%)   2/60 (3%)    1/62 (2%)    0/100 (0%) |  1/142 (1%)   1/62 (2%)    2/63 (3%)    0/99 (0%)  |
|ADJUSTED (b)           |   0.0%         4.6%         2.2%         0.0%      |   1.9%         2.6%         5.6%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    1/39 (3%)    0/37 (0%)    0/65 (0%)  |  1/53 (2%)    1/38 (3%)    1/34 (3%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          619          579          ---       |   729 (T)      729 (T)      724          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.376N     P=0.143      P=0.368        (e)      |  P=0.386N     P=0.686      P=0.355      P=0.504N   |
|INCIDENTAL TUMOR       |  P=0.551N     P=0.069      P=0.331        (e)      |  P=0.452N     P=0.686      P=0.264      P=0.504N   |
|LOGISTIC REGRESSION    |  P=0.414N     P=0.108      P=0.344        (e)      |  P=0.398N     P=0.686      P=0.329      P=0.504N   |
|COCHRAN-ARMITAGE       |  P=0.417N                                          |  P=0.465N                                          |
|FISHER EXACT           |               P=0.098      P=0.321        (e)      |               P=0.517      P=0.224      P=0.589N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/131 (5%)   2/60 (3%)    0/62 (0%)    2/100 (2%) |  5/142 (4%)   2/62 (3%)    7/63 (11%)   2/99 (2%)  |
|ADJUSTED (b)           |  11.3%         5.1%         0.0%         2.7%      |   7.0%         5.3%        18.4%         3.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/10 (10%) |  0/10 (0%)    0/8 (0%)     1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |  4/58 (7%)    2/39 (5%)    0/37 (0%)    1/65 (2%)  |  2/53 (4%)    2/38 (5%)    5/34 (15%)   1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |   698          729 (T)      ---          458 (I)   |   420          729 (T)      459 (I)      712       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.034N*    P=0.224N     P=0.043N*    P=0.069N   |  P=0.428N     P=0.431N     P=0.123      P=0.286N   |
|INCIDENTAL TUMOR       |  P=0.073N     P=0.335N     P=0.088N     P=0.161N   |  P=0.552      P=0.586N     P=0.058      P=0.483N   |
|LOGISTIC REGRESSION    |  P=0.058N     P=0.256N     P=0.051N     P=0.129N   |  P=0.532N     P=0.561N     P=0.049 *    P=0.365N   |
|COCHRAN-ARMITAGE       |  P=0.074N                                          |  P=0.551N                                          |
|FISHER EXACT           |               P=0.422N     P=0.063N     P=0.170N   |               P=0.639N     P=0.039 *    P=0.395N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   4
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/131 (6%)   3/60 (5%)    0/62 (0%)    3/100 (3%) |  6/142 (4%)   3/62 (5%)    7/63 (11%)   2/99 (2%)  |
|ADJUSTED (b)           |  13.0%         7.1%         0.0%         4.2%      |   8.8%         7.5%        18.4%         3.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/10 (10%) |  0/10 (0%)    0/8 (0%)     1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |  5/58 (9%)    2/39 (5%)    0/37 (0%)    2/65 (3%)  |  3/53 (6%)    2/38 (5%)    5/34 (15%)   1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |   698          540          ---          458 (I)   |   420          648          459 (I)      712       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.041N*    P=0.298N     P=0.028N*    P=0.083N   |  P=0.282N     P=0.499N     P=0.187      P=0.188N   |
|INCIDENTAL TUMOR       |  P=0.094N     P=0.486N     P=0.058N     P=0.176N   |  P=0.414N     P=0.603      P=0.102      P=0.338N   |
|LOGISTIC REGRESSION    |  P=0.073N     P=0.382N     P=0.034N*    P=0.157N   |  P=0.379N     P=0.640N     P=0.085      P=0.259N   |
|COCHRAN-ARMITAGE       |  P=0.090N                                          |  P=0.402N                                          |
|FISHER EXACT           |               P=0.527N     P=0.042N*    P=0.218N   |               P=0.550      P=0.064      P=0.290N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Duodenum                                                                                                        |
|     Polyp Adenomatous                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/131 (0%)   0/60 (0%)    2/62 (3%)    1/100 (1%) |  0/142 (0%)   0/62 (0%)    0/63 (0%)    0/99 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         5.4%         1.5%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    0/39 (0%)    2/37 (5%)    1/65 (2%)  |  0/53 (0%)    0/38 (0%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.227        (e)        P=0.147      P=0.523    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.227        (e)        P=0.147      P=0.523    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.227        (e)        P=0.147      P=0.523    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.166                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.102      P=0.433    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   5
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/130 (0%)   0/60 (0%)    0/62 (0%)    2/100 (2%) |  1/140 (1%)   1/62 (2%)    1/62 (2%)    1/99 (1%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         3.1%      |   1.9%         2.2%         2.9%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    0/39 (0%)    0/37 (0%)    2/65 (3%)  |  1/53 (2%)    0/38 (0%)    1/34 (3%)    1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          729 (T)   |   729 (T)      617          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.074        (e)          (e)        P=0.264    |  P=0.597      P=0.658      P=0.659      P=0.757    |
|INCIDENTAL TUMOR       |  P=0.074        (e)          (e)        P=0.264    |  P=0.568      P=0.583      P=0.659      P=0.757    |
|LOGISTIC REGRESSION    |  P=0.074        (e)          (e)        P=0.264    |  P=0.563      P=0.611      P=0.659      P=0.757    |
|COCHRAN-ARMITAGE       |  P=0.052                                           |  P=0.538                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.188    |               P=0.521      P=0.521      P=0.658    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/131 (4%)   1/60 (2%)    2/62 (3%)    3/100 (3%) |  3/142 (2%)   0/62 (0%)    0/63 (0%)    1/99 (1%)  |
|ADJUSTED (b)           |   5.8%         2.6%         5.4%         4.0%      |   4.0%         0.0%         0.0%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/58 (2%)    1/39 (3%)    2/37 (5%)    1/65 (2%)  |  1/53 (2%)    0/38 (0%)    0/34 (0%)    1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      729 (T)      729 (T)      386       |   518          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.405N     P=0.197N     P=0.409N     P=0.390N   |  P=0.297N     P=0.234N     P=0.256N     P=0.369N   |
|INCIDENTAL TUMOR       |  P=0.543      P=0.292N     P=0.530N     P=0.639    |  P=0.399N     P=0.350N     P=0.345N     P=0.513N   |
|LOGISTIC REGRESSION    |  P=0.506N     P=0.387N     P=0.580N     P=0.526N   |  P=0.331N     P=0.295N     P=0.291N     P=0.432N   |
|COCHRAN-ARMITAGE       |  P=0.504N                                          |  P=0.334N                                          |
|FISHER EXACT           |               P=0.387N     P=0.599N     P=0.517N   |               P=0.335N     P=0.330N     P=0.456N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   6
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatoblastoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/131 (0%)   1/60 (2%)    1/62 (2%)    3/100 (3%) |  0/142 (0%)   1/62 (2%)    0/63 (0%)    2/99 (2%)  |
|ADJUSTED (b)           |   0.0%         2.6%         2.7%         4.4%      |   0.0%         2.6%         0.0%         3.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    1/39 (3%)    1/37 (3%)    1/65 (2%)  |  0/53 (0%)    1/38 (3%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      729 (T)      705       |   ---          729 (T)      ---          477       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.101      P=0.421      P=0.410      P=0.142    |  P=0.174      P=0.434        (e)        P=0.192    |
|INCIDENTAL TUMOR       |  P=0.041 *    P=0.421      P=0.410      P=0.030 *  |  P=0.072      P=0.434        (e)        P=0.030 *  |
|LOGISTIC REGRESSION    |  P=0.082      P=0.421      P=0.410      P=0.109    |  P=0.150      P=0.434        (e)        P=0.164    |
|COCHRAN-ARMITAGE       |  P=0.059                                           |  P=0.150                                           |
|FISHER EXACT           |               P=0.314      P=0.321      P=0.080    |               P=0.304        (e)        P=0.168    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 69/131 (53%) 39/60 (65%)  32/62 (52%)  58/100 (58%)| 61/142 (43%) 32/62 (52%)  26/63 (41%)  36/99 (36%) |
|ADJUSTED (b)           |  81.1%        76.1%        75.7%        79.1%      |  82.5%        70.4%        62.6%        61.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  4/10 (40%)   5/10 (50%)   2/9 (22%)    5/10 (50%) |  3/10 (30%)   4/8 (50%)    3/10 (30%)   2/9 (22%)  |
|TERMINAL (d)           | 43/58 (74%)  27/39 (69%)  27/37 (73%)  50/65 (77%) | 41/53 (77%)  25/38 (66%)  19/34 (56%)  30/52 (58%) |
|FIRST INCIDENCE (DAYS) |   420          458 (I)      459 (I)      458 (I)   |   358          458 (I)      458 (I)      459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.024N*    P=0.148N     P=0.031N*    P=0.026N*  |  P=0.001N**   P=0.044N*    P=0.011N*    P=0.001N** |
|INCIDENTAL TUMOR       |  P=0.300N     P=0.428      P=0.150N     P=0.423N   |  P=0.009N**   P=0.250N     P=0.067N     P=0.014N*  |
|LOGISTIC REGRESSION    |  P=0.476N     P=0.294      P=0.292N     P=0.472    |  P=0.034N*    P=0.562N     P=0.181N     P=0.050N*  |
|COCHRAN-ARMITAGE       |  P=0.412                                           |  P=0.091N                                          |
|FISHER EXACT           |               P=0.075      P=0.506N     P=0.251    |               P=0.161      P=0.472N     P=0.186N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   7
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/131 (24%) 15/60 (25%)  14/62 (23%)  15/100 (15%)| 17/142 (12%) 11/62 (18%)   8/63 (13%)  13/99 (13%) |
|ADJUSTED (b)           |  41.1%        33.9%        31.2%        20.6%      |  26.1%        27.5%        20.7%        23.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/9 (11%)    0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    1/9 (11%)  |
|TERMINAL (d)           | 15/58 (26%)  10/39 (26%)   7/37 (19%)   8/65 (12%) |  9/53 (17%)   9/38 (24%)   5/34 (15%)  10/52 (19%) |
|FIRST INCIDENCE (DAYS) |   519          624          459 (I)      529       |   602          678          527          459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006N**   P=0.188N     P=0.194N     P=0.005N** |  P=0.276N     P=0.539N     P=0.353N     P=0.360N   |
|INCIDENTAL TUMOR       |  P=0.167N     P=0.495      P=0.550      P=0.204N   |  P=0.504N     P=0.319      P=0.554      P=0.553    |
|LOGISTIC REGRESSION    |  P=0.100N     P=0.545N     P=0.477N     P=0.135N   |  P=0.428N     P=0.426      P=0.501N     P=0.566N   |
|COCHRAN-ARMITAGE       |  P=0.041N*                                         |  P=0.514N                                          |
|FISHER EXACT           |               P=0.534      P=0.465N     P=0.054N   |               P=0.188      P=0.525      P=0.469    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/131 (24%) 16/60 (27%)  14/62 (23%)  17/100 (17%)| 17/142 (12%) 12/62 (19%)   8/63 (13%)  15/99 (15%) |
|ADJUSTED (b)           |  41.1%        36.1%        31.2%        23.2%      |  26.1%        30.0%        20.7%        25.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/9 (11%)    0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    1/9 (11%)  |
|TERMINAL (d)           | 15/58 (26%)  11/39 (28%)   7/37 (19%)   9/65 (14%) |  9/53 (17%)  10/38 (26%)   5/34 (15%)  10/52 (19%) |
|FIRST INCIDENCE (DAYS) |   519          624          459 (I)      529       |   602          678          527          459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.011N*    P=0.245N     P=0.194N     P=0.012N*  |  P=0.398N     P=0.530      P=0.353N     P=0.528N   |
|INCIDENTAL TUMOR       |  P=0.265N     P=0.403      P=0.550      P=0.359N   |  P=0.384      P=0.234      P=0.554      P=0.308    |
|LOGISTIC REGRESSION    |  P=0.161N     P=0.515      P=0.477N     P=0.238N   |  P=0.486      P=0.323      P=0.501N     P=0.398    |
|COCHRAN-ARMITAGE       |  P=0.076N                                          |  P=0.411                                           |
|FISHER EXACT           |               P=0.436      P=0.465N     P=0.113N   |               P=0.122      P=0.525      P=0.299    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   8
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 84/131 (64%) 44/60 (73%)  40/62 (65%)  66/100 (66%)| 68/142 (48%) 37/62 (60%)  29/63 (46%)  44/99 (44%) |
|ADJUSTED (b)           |  89.0%        84.4%        84.9%        83.4%      |  86.4%        80.0%        66.7%        73.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  4/10 (40%)   5/10 (50%)   3/9 (33%)    5/10 (50%) |  3/10 (30%)   4/8 (50%)    3/10 (30%)   3/9 (33%)  |
|TERMINAL (d)           | 48/58 (83%)  31/39 (79%)  30/37 (81%)  52/65 (80%) | 43/53 (81%)  29/38 (76%)  20/34 (59%)  36/52 (69%) |
|FIRST INCIDENCE (DAYS) |   420          458 (I)      459 (I)      458 (I)   |   358          458 (I)      458 (I)      459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006N**   P=0.043N*    P=0.031N*    P=0.004N** |  P=0.003N**   P=0.057N     P=0.009N**   P=0.003N** |
|INCIDENTAL TUMOR       |  P=0.379N     P=0.555      P=0.329N     P=0.472N   |  P=0.029N*    P=0.417N     P=0.085N     P=0.048N*  |
|LOGISTIC REGRESSION    |  P=0.308N     P=0.545      P=0.318N     P=0.395N   |  P=0.071N     P=0.452      P=0.157N     P=0.128N   |
|COCHRAN-ARMITAGE       |  P=0.489N                                          |  P=0.166N                                          |
|FISHER EXACT           |               P=0.137      P=0.545      P=0.438    |               P=0.081      P=0.463N     P=0.346N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 84/131 (64%) 44/60 (73%)  40/62 (65%)  66/100 (66%)| 68/142 (48%) 37/62 (60%)  29/63 (46%)  45/99 (45%) |
|ADJUSTED (b)           |  89.0%        84.4%        84.9%        83.4%      |  86.4%        80.0%        66.7%        73.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  4/10 (40%)   5/10 (50%)   3/9 (33%)    5/10 (50%) |  3/10 (30%)   4/8 (50%)    3/10 (30%)   3/9 (33%)  |
|TERMINAL (d)           | 48/58 (83%)  31/39 (79%)  30/37 (81%)  52/65 (80%) | 43/53 (81%)  29/38 (76%)  20/34 (59%)  36/52 (69%) |
|FIRST INCIDENCE (DAYS) |   420          458 (I)      459 (I)      458 (I)   |   358          458 (I)      458 (I)      459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006N**   P=0.043N*    P=0.031N*    P=0.004N** |  P=0.005N**   P=0.057N     P=0.009N**   P=0.006N** |
|INCIDENTAL TUMOR       |  P=0.379N     P=0.555      P=0.329N     P=0.472N   |  P=0.049N*    P=0.417N     P=0.085N     P=0.083N   |
|LOGISTIC REGRESSION    |  P=0.308N     P=0.545      P=0.318N     P=0.395N   |  P=0.102N     P=0.452      P=0.157N     P=0.181N   |
|COCHRAN-ARMITAGE       |  P=0.489N                                          |  P=0.206N                                          |
|FISHER EXACT           |               P=0.137      P=0.545      P=0.438    |               P=0.081      P=0.463N     P=0.405N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE   9
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/131 (10%)  4/60 (7%)   13/62 (21%)  11/100 (11%)|  7/142 (5%)   4/62 (6%)    2/63 (3%)    4/99 (4%)  |
|ADJUSTED (b)           |  20.8%        10.3%        32.4%        16.6%      |  10.7%         9.6%         5.9%         7.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    1/9 (11%)    0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           | 11/58 (19%)   4/39 (10%)  11/37 (30%)  10/65 (15%) |  3/53 (6%)    2/38 (5%)    2/34 (6%)    4/52 (8%)  |
|FIRST INCIDENCE (DAYS) |   459 (I)      729 (T)      459 (I)      691       |   456          617          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.491      P=0.102N     P=0.151      P=0.316N   |  P=0.216N     P=0.550N     P=0.269N     P=0.319N   |
|INCIDENTAL TUMOR       |  P=0.412      P=0.114N     P=0.109      P=0.395N   |  P=0.353N     P=0.422      P=0.414N     P=0.505N   |
|LOGISTIC REGRESSION    |  P=0.299      P=0.189N     P=0.051      P=0.514N   |  P=0.290N     P=0.564      P=0.354N     P=0.436N   |
|COCHRAN-ARMITAGE       |  P=0.208                                           |  P=0.328N                                          |
|FISHER EXACT           |               P=0.332N     P=0.033 *    P=0.478    |               P=0.442      P=0.440N     P=0.502N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/131 (12%)  9/60 (15%)   1/62 (2%)    7/100 (7%) |  3/142 (2%)   2/62 (3%)    2/63 (3%)    3/99 (3%)  |
|ADJUSTED (b)           |  23.1%        21.7%         2.7%        10.4%      |   5.1%         5.3%         5.6%         5.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           | 10/58 (17%)   7/39 (18%)   1/37 (3%)    6/65 (9%)  |  1/53 (2%)    2/38 (5%)    1/34 (3%)    3/52 (6%)  |
|FIRST INCIDENCE (DAYS) |   433          656          729 (T)      593       |   691          729 (T)      724          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006N**   P=0.453N     P=0.006N**   P=0.031N*  |  P=0.534      P=0.669N     P=0.655      P=0.637    |
|INCIDENTAL TUMOR       |  P=0.025N*    P=0.467      P=0.011N*    P=0.130N   |  P=0.411      P=0.549      P=0.469      P=0.505    |
|LOGISTIC REGRESSION    |  P=0.016N*    P=0.552      P=0.010N*    P=0.088N   |  P=0.495      P=0.636      P=0.607      P=0.587    |
|COCHRAN-ARMITAGE       |  P=0.028N*                                         |  P=0.414                                           |
|FISHER EXACT           |               P=0.375      P=0.010N**   P=0.138N   |               P=0.481      P=0.488      P=0.478    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  10
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 29/131 (22%) 13/60 (22%)  14/62 (23%)  18/100 (18%)| 10/142 (7%)   6/62 (10%)   4/63 (6%)    7/99 (7%)  |
|ADJUSTED (b)           |  42.1%        31.5%        35.0%        26.7%      |  15.3%        14.7%        11.4%        13.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    1/9 (11%)    0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           | 21/58 (36%)  11/39 (28%)  12/37 (32%)  16/65 (25%) |  4/53 (8%)    4/38 (11%)   3/34 (9%)    7/52 (13%) |
|FIRST INCIDENCE (DAYS) |   433          656          459 (I)      593       |   456          617          724          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.038N*    P=0.125N     P=0.225N     P=0.026N*  |  P=0.280N     P=0.537N     P=0.324N     P=0.364N   |
|INCIDENTAL TUMOR       |  P=0.119N     P=0.270N     P=0.358N     P=0.109N   |  P=0.477N     P=0.349      P=0.570N     P=0.604    |
|LOGISTIC REGRESSION    |  P=0.146N     P=0.300N     P=0.479N     P=0.129N   |  P=0.382N     P=0.515      P=0.438N     P=0.509N   |
|COCHRAN-ARMITAGE       |  P=0.256N                                          |  P=0.452N                                          |
|FISHER EXACT           |               P=0.551N     P=0.541      P=0.272N   |               P=0.349      P=0.560N     P=0.592    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  3/139 (2%)   1/60 (2%)    0/63 (0%)    2/99 (2%)  |
|ADJUSTED (b)           |                                                    |   5.7%         2.8%         0.0%         3.2%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/8 (0%)     0/10 (0%)    1/9 (11%)  |
|TERMINAL (d)           |                                                    |  3/53 (6%)    1/36 (3%)    0/34 (0%)    1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   729 (T)      729 (T)      ---          459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.398N     P=0.451N     P=0.210N     P=0.516N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.398N     P=0.451N     P=0.210N     P=0.516N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.472N     P=0.451N     P=0.210N     P=0.625N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.489N                                          |
|FISHER EXACT           |                                                    |               P=0.649N     P=0.324N     P=0.656N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  11
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/123 (0%)   0/59 (0%)    0/59 (0%)    0/95 (0%)  | 28/141 (20%)  7/61 (11%)   8/63 (13%)  13/98 (13%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  42.3%        17.4%        23.5%        24.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/53 (0%)    0/38 (0%)    0/36 (0%)    0/61 (0%)  | 18/53 (34%)   5/37 (14%)   8/34 (24%)  12/52 (23%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   528          534          729 (T)      606       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.030N*    P=0.008N**   P=0.023N*    P=0.014N*  |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.080N     P=0.038N*    P=0.057N     P=0.050N*  |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.066N     P=0.026N*    P=0.051N     P=0.045N*  |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.131N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.105N     P=0.149N     P=0.123N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/131 (1%)   0/60 (0%)    0/62 (0%)    0/100 (0%) |  4/142 (3%)   2/62 (3%)    0/63 (0%)    5/99 (5%)  |
|ADJUSTED (b)           |   1.0%         0.0%         0.0%         0.0%      |   6.0%         4.3%         0.0%         9.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    0/39 (0%)    0/37 (0%)    0/65 (0%)  |  1/53 (2%)    1/38 (3%)    0/34 (0%)    4/52 (8%)  |
|FIRST INCIDENCE (DAYS) |   523          ---          ---          ---       |   603          395          ---          705       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.320N     P=0.636N     P=0.640N     P=0.546N   |  P=0.385      P=0.575N     P=0.160N     P=0.455    |
|INCIDENTAL TUMOR       |  P=0.451N     P=0.952N     P=0.860N     P=0.734N   |  P=0.219      P=0.528      P=0.268N     P=0.260    |
|LOGISTIC REGRESSION    |  P=0.326N     P=0.709N     P=0.665N     P=0.564N   |  P=0.307      P=0.652      P=0.184N     P=0.356    |
|COCHRAN-ARMITAGE       |  P=0.323N                                          |  P=0.292                                           |
|FISHER EXACT           |               P=0.686N     P=0.679N     P=0.567N   |               P=0.591      P=0.227N     P=0.286    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  12
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/131 (2%)   1/60 (2%)    0/62 (0%)    2/100 (2%) |  1/142 (1%)   0/62 (0%)    0/63 (0%)    0/99 (0%)  |
|ADJUSTED (b)           |   2.1%         2.6%         0.0%         2.9%      |   1.7%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    1/39 (3%)    0/37 (0%)    1/65 (2%)  |  0/53 (0%)    0/38 (0%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   496          729 (T)      ---          684       |   713          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.572N     P=0.698N     P=0.402N     P=0.658    |  P=0.308N     P=0.591N     P=0.602N     P=0.525N   |
|INCIDENTAL TUMOR       |  P=0.406      P=0.588      P=0.547N     P=0.361    |  P=0.418N     P=0.791N     P=0.757N     P=0.701N   |
|LOGISTIC REGRESSION    |  P=0.551      P=0.701      P=0.431N     P=0.595    |  P=0.317N     P=0.610N     P=0.622N     P=0.540N   |
|COCHRAN-ARMITAGE       |  P=0.547                                           |  P=0.335N                                          |
|FISHER EXACT           |               P=0.680      P=0.460N     P=0.582    |               P=0.696N     P=0.693N     P=0.589N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/131 (1%)   0/60 (0%)    0/62 (0%)    0/100 (0%) |  4/142 (3%)   2/62 (3%)    0/63 (0%)    6/99 (6%)  |
|ADJUSTED (b)           |   1.0%         0.0%         0.0%         0.0%      |   6.0%         4.3%         0.0%        10.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    0/39 (0%)    0/37 (0%)    0/65 (0%)  |  1/53 (2%)    1/38 (3%)    0/34 (0%)    4/52 (8%)  |
|FIRST INCIDENCE (DAYS) |   523          ---          ---          ---       |   603          395          ---          566       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.320N     P=0.636N     P=0.640N     P=0.546N   |  P=0.242      P=0.575N     P=0.160N     P=0.318    |
|INCIDENTAL TUMOR       |  P=0.451N     P=0.952N     P=0.860N     P=0.734N   |  P=0.110      P=0.528      P=0.268N     P=0.141    |
|LOGISTIC REGRESSION    |  P=0.326N     P=0.709N     P=0.665N     P=0.564N   |  P=0.178      P=0.652      P=0.184N     P=0.219    |
|COCHRAN-ARMITAGE       |  P=0.323N                                          |  P=0.171                                           |
|FISHER EXACT           |               P=0.686N     P=0.679N     P=0.567N   |               P=0.591      P=0.227N     P=0.180    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  13
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/131 (1%)   0/60 (0%)    0/62 (0%)    0/100 (0%) |  4/142 (3%)   2/62 (3%)    0/63 (0%)    6/99 (6%)  |
|ADJUSTED (b)           |   1.0%         0.0%         0.0%         0.0%      |   6.0%         4.3%         0.0%        10.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    0/39 (0%)    0/37 (0%)    0/65 (0%)  |  1/53 (2%)    1/38 (3%)    0/34 (0%)    4/52 (8%)  |
|FIRST INCIDENCE (DAYS) |   523          ---          ---          ---       |   603          395          ---          566       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.320N     P=0.636N     P=0.640N     P=0.546N   |  P=0.242      P=0.575N     P=0.160N     P=0.318    |
|INCIDENTAL TUMOR       |  P=0.451N     P=0.952N     P=0.860N     P=0.734N   |  P=0.110      P=0.528      P=0.268N     P=0.141    |
|LOGISTIC REGRESSION    |  P=0.326N     P=0.709N     P=0.665N     P=0.564N   |  P=0.178      P=0.652      P=0.184N     P=0.219    |
|COCHRAN-ARMITAGE       |  P=0.323N                                          |  P=0.171                                           |
|FISHER EXACT           |               P=0.686N     P=0.679N     P=0.567N   |               P=0.591      P=0.227N     P=0.180    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/131 (2%)   0/60 (0%)    0/62 (0%)    1/100 (1%) |  3/142 (2%)   4/62 (6%)    2/63 (3%)    4/99 (4%)  |
|ADJUSTED (b)           |   2.2%         0.0%         0.0%         1.5%      |   5.0%        10.5%         5.9%         6.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    0/39 (0%)    0/37 (0%)    1/65 (2%)  |  2/53 (4%)    4/38 (11%)   2/34 (6%)    2/52 (4%)  |
|FIRST INCIDENCE (DAYS) |   523          ---          ---          729 (T)   |   644          729 (T)      729 (T)      477       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.456N     P=0.385N     P=0.398N     P=0.529N   |  P=0.510      P=0.309      P=0.649      P=0.427    |
|INCIDENTAL TUMOR       |  P=0.617      P=0.708N     P=0.547N     P=0.719    |  P=0.424      P=0.263      P=0.603      P=0.280    |
|LOGISTIC REGRESSION    |  P=0.495N     P=0.452N     P=0.424N     P=0.591N   |  P=0.425      P=0.232      P=0.597      P=0.334    |
|COCHRAN-ARMITAGE       |  P=0.495N                                          |  P=0.396                                           |
|FISHER EXACT           |               P=0.469N     P=0.460N     P=0.600N   |               P=0.127      P=0.488      P=0.309    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  14
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/131 (2%)   1/60 (2%)    3/62 (5%)    2/100 (2%) |  6/142 (4%)   0/62 (0%)    0/63 (0%)    2/99 (2%)  |
|ADJUSTED (b)           |   3.1%         2.6%         8.1%         3.1%      |   8.5%         0.0%         0.0%         3.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/58 (2%)    1/39 (3%)    3/37 (8%)    2/65 (3%)  |  2/53 (4%)    0/38 (0%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   684          729 (T)      729 (T)      729 (T)   |   420          ---          ---          707       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.509      P=0.650N     P=0.290      P=0.663N   |  P=0.167N     P=0.068N     P=0.079N     P=0.196N   |
|INCIDENTAL TUMOR       |  P=0.449      P=0.722N     P=0.223      P=0.636    |  P=0.362N     P=0.150N     P=0.145N     P=0.488N   |
|LOGISTIC REGRESSION    |  P=0.462      P=0.688N     P=0.245      P=0.672    |  P=0.206N     P=0.098N     P=0.101N     P=0.262N   |
|COCHRAN-ARMITAGE       |  P=0.374                                           |  P=0.214N                                          |
|FISHER EXACT           |               P=0.680      P=0.190      P=0.582    |               P=0.110N     P=0.107N     P=0.290N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/131 (2%)   1/60 (2%)    3/62 (5%)    2/100 (2%) |  6/142 (4%)   1/62 (2%)    0/63 (0%)    2/99 (2%)  |
|ADJUSTED (b)           |   3.1%         2.6%         8.1%         3.1%      |   8.5%         1.9%         0.0%         3.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    1/8 (13%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/58 (2%)    1/39 (3%)    3/37 (8%)    2/65 (3%)  |  2/53 (4%)    0/38 (0%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   684          729 (T)      729 (T)      729 (T)   |   420          459 (I)      ---          707       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.509      P=0.650N     P=0.290      P=0.663N   |  P=0.126N     P=0.173N     P=0.079N     P=0.196N   |
|INCIDENTAL TUMOR       |  P=0.449      P=0.722N     P=0.223      P=0.636    |  P=0.282N     P=0.326N     P=0.145N     P=0.488N   |
|LOGISTIC REGRESSION    |  P=0.462      P=0.688N     P=0.245      P=0.672    |  P=0.168N     P=0.284N     P=0.101N     P=0.262N   |
|COCHRAN-ARMITAGE       |  P=0.374                                           |  P=0.171N                                          |
|FISHER EXACT           |               P=0.680      P=0.190      P=0.582    |               P=0.317N     P=0.107N     P=0.290N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  15
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/142 (1%)   0/62 (0%)    0/63 (0%)    0/99 (0%)  |
|ADJUSTED (b)           |                                                    |   3.6%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |                                                    |  1/53 (2%)    0/38 (0%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   722          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.134N     P=0.322N     P=0.341N     P=0.250N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.184N     P=0.435N     P=0.435N     P=0.347N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.140N     P=0.344N     P=0.360N     P=0.262N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.167N                                          |
|FISHER EXACT           |                                                    |               P=0.483N     P=0.479N     P=0.346N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  3/142 (2%)   1/62 (2%)    1/63 (2%)    1/99 (1%)  |
|ADJUSTED (b)           |                                                    |   4.7%         2.6%         2.5%         1.2%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  1/10 (10%)   0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |                                                    |  2/53 (4%)    1/38 (3%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   459 (I)      729 (T)      653          349       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.274N     P=0.420N     P=0.443N     P=0.356N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.314N     P=0.420N     P=0.502N     P=0.357N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.336N     P=0.571N     P=0.590N     P=0.443N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.336N                                          |
|FISHER EXACT           |                                                    |               P=0.645N     P=0.639N     P=0.456N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  16
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  3/142 (2%)   1/62 (2%)    1/63 (2%)    2/99 (2%)  |
|ADJUSTED (b)           |                                                    |   4.7%         2.6%         2.5%         3.1%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  1/10 (10%)   0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |                                                    |  2/53 (4%)    1/38 (3%)    0/34 (0%)    1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   459 (I)      729 (T)      653          349       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.486N     P=0.420N     P=0.443N     P=0.550N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.526N     P=0.420N     P=0.502N     P=0.551N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.563N     P=0.571N     P=0.590N     P=0.657N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.564N                                          |
|FISHER EXACT           |                                                    |               P=0.645N     P=0.639N     P=0.665N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/131 (0%)   1/60 (2%)    0/62 (0%)    0/100 (0%) |  4/142 (3%)   2/62 (3%)    0/63 (0%)    2/99 (2%)  |
|ADJUSTED (b)           |   0.0%         2.6%         0.0%         0.0%      |   6.6%         5.3%         0.0%         3.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    1/39 (3%)    0/37 (0%)    0/65 (0%)  |  2/53 (4%)    2/38 (5%)    0/34 (0%)    1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   592          729 (T)      ---          709       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.403N     P=0.421        (e)          (e)      |  P=0.214N     P=0.527N     P=0.149N     P=0.381N   |
|INCIDENTAL TUMOR       |  P=0.403N     P=0.421        (e)          (e)      |  P=0.303N     P=0.651N     P=0.216N     P=0.555N   |
|LOGISTIC REGRESSION    |  P=0.403N     P=0.421        (e)          (e)      |  P=0.253N     P=0.618N     P=0.178N     P=0.453N   |
|COCHRAN-ARMITAGE       |  P=0.452N                                          |  P=0.291N                                          |
|FISHER EXACT           |               P=0.314        (e)          (e)      |               P=0.591      P=0.227N     P=0.522N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  17
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/131 (5%)   5/60 (8%)    4/62 (6%)    6/100 (6%) |  7/142 (5%)   3/62 (5%)    4/63 (6%)    1/99 (1%)  |
|ADJUSTED (b)           |   7.7%        12.1%        10.1%         8.3%      |   9.5%         7.7%        11.4%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/10 (0%)    0/9 (0%)     0/10 (0%)  |  1/10 (10%)   0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/58 (2%)    4/39 (10%)   3/37 (8%)    3/65 (5%)  |  2/53 (4%)    2/38 (5%)    3/34 (9%)    1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      619          579          386       |   458 (I)      698          724          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.401N     P=0.560      P=0.578N     P=0.539N   |  P=0.060N     P=0.387N     P=0.567N     P=0.056N   |
|INCIDENTAL TUMOR       |  P=0.395      P=0.301      P=0.509      P=0.302    |  P=0.133N     P=0.632N     P=0.501      P=0.130N   |
|LOGISTIC REGRESSION    |  P=0.543N     P=0.317      P=0.507      P=0.522    |  P=0.094N     P=0.556N     P=0.531      P=0.089N   |
|COCHRAN-ARMITAGE       |  P=0.539                                           |  P=0.108N                                          |
|FISHER EXACT           |               P=0.310      P=0.494      P=0.524    |               P=0.641N     P=0.452      P=0.092N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/131 (5%)   6/60 (10%)   4/62 (6%)    6/100 (6%) | 11/142 (8%)   5/62 (8%)    4/63 (6%)    3/99 (3%)  |
|ADJUSTED (b)           |   7.7%        14.6%        10.1%         8.3%      |  15.6%        12.8%        11.4%         5.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/10 (0%)    0/9 (0%)     0/10 (0%)  |  1/10 (10%)   0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/58 (2%)    5/39 (13%)   3/37 (8%)    3/65 (5%)  |  4/53 (8%)    4/38 (11%)   3/34 (9%)    2/52 (4%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      619          579          386       |   458 (I)      698          724          709       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.342N     P=0.420      P=0.578N     P=0.539N   |  P=0.032N*    P=0.327N     P=0.251N     P=0.047N*  |
|INCIDENTAL TUMOR       |  P=0.465      P=0.189      P=0.509      P=0.302    |  P=0.090N     P=0.591N     P=0.451N     P=0.145N   |
|LOGISTIC REGRESSION    |  P=0.486N     P=0.197      P=0.507      P=0.522    |  P=0.057N     P=0.515N     P=0.392N     P=0.086N   |
|COCHRAN-ARMITAGE       |  P=0.495N                                          |  P=0.073N                                          |
|FISHER EXACT           |               P=0.188      P=0.494      P=0.524    |               P=0.569      P=0.488N     P=0.101N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  18
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/131 (2%)   0/60 (0%)    2/62 (3%)    2/100 (2%) |  5/142 (4%)   3/62 (5%)    2/63 (3%)    5/99 (5%)  |
|ADJUSTED (b)           |   2.6%         0.0%         5.1%         2.9%      |   7.4%         7.2%         4.9%         8.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/58 (2%)    0/39 (0%)    1/37 (3%)    1/65 (2%)  |  2/53 (4%)    2/38 (5%)    0/34 (0%)    1/52 (2%)  |
|FIRST INCIDENCE (DAYS) |   359          ---          651          623       |   562          584          587          584       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.390      P=0.364N     P=0.481      P=0.677    |  P=0.466      P=0.617N     P=0.497N     P=0.512    |
|INCIDENTAL TUMOR       |  P=0.215      P=0.456N     P=0.380      P=0.455    |  P=0.265      P=0.494      P=0.618      P=0.281    |
|LOGISTIC REGRESSION    |  P=0.322      P=0.466N     P=0.410      P=0.593    |  P=0.190      P=0.564      P=0.568N     P=0.195    |
|COCHRAN-ARMITAGE       |  P=0.319                                           |  P=0.386                                           |
|FISHER EXACT           |               P=0.469N     P=0.386      P=0.582    |               P=0.459      P=0.631N     P=0.393    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/131 (5%)   1/60 (2%)    8/62 (13%)   3/100 (3%) | 17/142 (12%)  8/62 (13%)  13/63 (21%)  24/99 (24%) |
|ADJUSTED (b)           |   9.8%         2.6%        20.9%         4.4%      |  26.8%        19.3%        33.2%        38.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  3/58 (5%)    1/39 (3%)    7/37 (19%)   2/65 (3%)  | 10/53 (19%)   6/38 (16%)   9/34 (26%)  15/52 (29%) |
|FIRST INCIDENCE (DAYS) |   359          729 (T)      651          623       |   562          584          379          241       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.363N     P=0.126N     P=0.152      P=0.167N   |  P=0.024 *    P=0.261N     P=0.322      P=0.092    |
|INCIDENTAL TUMOR       |  P=0.517      P=0.236N     P=0.069      P=0.454N   |  P=0.002 **   P=0.511N     P=0.112      P=0.010 *  |
|LOGISTIC REGRESSION    |  P=0.495N     P=0.186N     P=0.082      P=0.268N   |  P=0.005 **   P=0.434N     P=0.160      P=0.017 *  |
|COCHRAN-ARMITAGE       |  P=0.540N                                          |  P=0.004 **                                        |
|FISHER EXACT           |               P=0.223N     P=0.065      P=0.299N   |               P=0.509      P=0.082      P=0.011 *  |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  19
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/131 (4%)   1/60 (2%)    6/62 (10%)   1/100 (1%) | 12/142 (8%)   5/62 (8%)   11/63 (17%)  19/99 (19%) |
|ADJUSTED (b)           |   7.4%         2.6%        16.2%         1.5%      |  20.3%        12.4%        29.7%        32.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/58 (3%)    1/39 (3%)    6/37 (16%)   1/65 (2%)  |  8/53 (15%)   4/38 (11%)   9/34 (26%)  14/52 (27%) |
|FIRST INCIDENCE (DAYS) |   591          729 (T)      729 (T)      729 (T)   |   652          587          379          241       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.224N     P=0.244N     P=0.200      P=0.101N   |  P=0.016 *    P=0.237N     P=0.223      P=0.088    |
|INCIDENTAL TUMOR       |  P=0.335N     P=0.382N     P=0.119      P=0.247N   |  P=0.003 **   P=0.399N     P=0.103      P=0.020 *  |
|LOGISTIC REGRESSION    |  P=0.295N     P=0.299N     P=0.134      P=0.147N   |  P=0.004 **   P=0.352N     P=0.111      P=0.023 *  |
|COCHRAN-ARMITAGE       |  P=0.364N                                          |  P=0.003 **                                        |
|FISHER EXACT           |               P=0.387N     P=0.098      P=0.182N   |               P=0.584N     P=0.053      P=0.013 *  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/131 (0%)   1/60 (2%)    0/62 (0%)    0/100 (0%) |  2/142 (1%)   0/62 (0%)    0/63 (0%)    0/99 (0%)  |
|ADJUSTED (b)           |   0.0%         1.7%         0.0%         0.0%      |   2.7%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/8 (0%)     0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/58 (0%)    0/39 (0%)    0/37 (0%)    0/65 (0%)  |  1/53 (2%)    0/38 (0%)    0/34 (0%)    0/52 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          458 (I)      ---          ---       |   420          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.432N     P=0.500        (e)          (e)      |  P=0.149N     P=0.357N     P=0.374N     P=0.282N   |
|INCIDENTAL TUMOR       |  P=0.432N     P=0.500        (e)          (e)      |  P=0.208N     P=0.451N     P=0.443N     P=0.402N   |
|LOGISTIC REGRESSION    |  P=0.453N     P=0.252        (e)          (e)      |  P=0.167N     P=0.444N     P=0.435N     P=0.322N   |
|COCHRAN-ARMITAGE       |  P=0.452N                                          |  P=0.167N                                          |
|FISHER EXACT           |               P=0.314        (e)          (e)      |               P=0.483N     P=0.479N     P=0.346N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  20
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 79/131 (60%) 45/60 (75%)  38/62 (61%)  62/100 (62%)| 81/142 (57%) 38/62 (61%)  32/63 (51%)  48/99 (48%) |
|ADJUSTED (b)           |  88.2%        88.0%        86.0%        83.6%      |  93.8%        78.7%        73.8%        74.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  5/10 (50%)   5/10 (50%)   3/9 (33%)    5/10 (50%) |  4/10 (40%)   4/8 (50%)    3/10 (30%)   3/9 (33%)  |
|TERMINAL (d)           | 48/58 (83%)  33/39 (85%)  31/37 (84%)  53/65 (82%) | 48/53 (91%)  28/38 (74%)  23/34 (68%)  36/52 (69%) |
|FIRST INCIDENCE (DAYS) |   420          458 (I)      459 (I)      458 (I)   |   358          458 (I)      458 (I)      349       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002N**   P=0.117N     P=0.026N*    P=0.002N** |  P<0.001N**   P=0.004N**   P<0.001N**   P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.087N     P=0.369      P=0.211N     P=0.190N   |  P=0.012N*    P=0.111N     P=0.014N*    P=0.015N*  |
|LOGISTIC REGRESSION    |  P=0.216N     P=0.217      P=0.374N     P=0.384N   |  P=0.020N*    P=0.254N     P=0.039N*    P=0.030N*  |
|COCHRAN-ARMITAGE       |  P=0.395N                                          |  P=0.058N                                          |
|FISHER EXACT           |               P=0.034 *    P=0.512      P=0.451    |               P=0.341      P=0.249N     P=0.119N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 57/131 (44%) 32/60 (53%)  26/62 (42%)  33/100 (33%)| 44/142 (31%) 26/62 (42%)  25/63 (40%)  45/99 (45%) |
|ADJUSTED (b)           |  62.0%        65.1%        56.3%        42.8%      |  55.7%        57.1%        59.0%        63.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   1/10 (10%)   1/9 (11%)    0/10 (0%)  |  1/10 (10%)   1/8 (13%)    0/10 (0%)    1/9 (11%)  |
|TERMINAL (d)           | 25/58 (43%)  22/39 (56%)  17/37 (46%)  21/65 (32%) | 21/53 (40%)  19/38 (50%)  17/34 (50%)  27/52 (52%) |
|FIRST INCIDENCE (DAYS) |   359          458 (I)      459 (I)      386       |   420          395          379          241       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.290N     P=0.118N     P=0.002N** |  P=0.214      P=0.358N     P=0.450N     P=0.283    |
|INCIDENTAL TUMOR       |  P=0.129N     P=0.087      P=0.523      P=0.348N   |  P=0.006 **   P=0.190      P=0.160      P=0.005 ** |
|LOGISTIC REGRESSION    |  P=0.043N*    P=0.237      P=0.400N     P=0.114N   |  P=0.024 *    P=0.301      P=0.309      P=0.023 *  |
|COCHRAN-ARMITAGE       |  P=0.024N*                                         |  P=0.023 *                                         |
|FISHER EXACT           |               P=0.134      P=0.481N     P=0.068N   |               P=0.088      P=0.146      P=0.016 *  |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 02                                                 PAGE  21
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- SODIUM FLUORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   SPECIAL      25 PPM       100 PPM      175 PPM   |   SPECIAL      25 PPM       100 PPM      175 PPM   |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |101/131 (77%) 51/60 (85%)  47/62 (76%)  74/100 (74%)| 94/142 (66%) 45/62 (73%)  40/63 (63%)  65/99 (66%) |
|ADJUSTED (b)           |  94.3%        94.4%        93.9%        90.2%      |  96.8%        88.0%        84.8%        86.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/2 (0%)     0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  6/10 (60%)   6/10 (60%)   4/9 (44%)    5/10 (50%) |  5/10 (50%)   4/8 (50%)    3/10 (30%)   4/9 (44%)  |
|TERMINAL (d)           | 52/58 (90%)  36/39 (92%)  34/37 (92%)  57/65 (88%) | 50/53 (94%)  32/38 (84%)  27/34 (79%)  42/52 (81%) |
|FIRST INCIDENCE (DAYS) |   359          458 (I)      459 (I)      386       |   358          395          379          241       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.012N*    P=0.011N*    P<0.001N** |  P=0.015N*    P=0.004N**   P=0.002N**   P=0.010N** |
|INCIDENTAL TUMOR       |  P=0.166N     P=0.537      P=0.294N     P=0.335N   |  P=0.338N     P=0.229N     P=0.061N     P=0.381N   |
|LOGISTIC REGRESSION    |  P=0.069N     P=0.539N     P=0.181N     P=0.118N   |  P=0.302N     P=0.321N     P=0.076N     P=0.400N   |
|COCHRAN-ARMITAGE       |  P=0.182N                                          |  P=0.355N                                          |
|FISHER EXACT           |               P=0.143      P=0.489N     P=0.347N   |               P=0.232      P=0.412N     P=0.519N   |
|=================================================================================================================================|
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   165  458
          Female interim sacrifices(days): 165  458
 (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.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's 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. 
 (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).

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