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TR 393 Rat Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                       SODIUM FLUORIDE                                   DATE: 09/17/94       
EXPERIMENT: 05131 TEST: 01                                                                                     TIME: 04:23:52       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-55102          ROUTE: DOSED WATER                                                                 NTP C#: 55221B       
PATHOLOGIST: R. PERSING                      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: 01                                                                                     TIME: 04:23:52      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-55102          ROUTE: DOSED WATER                                                                 NTP C#: 55221B      
PATHOLOGIST: R. PERSING                      S. EUSTIS                                                         CAS: 7681-49-4      
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             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
                                                    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: 01                                                                                     TIME: 04:23:52       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-55102          ROUTE: DOSED WATER                                                                 NTP C#: 55221B       
PATHOLOGIST: R. PERSING                      S. EUSTIS                                                         CAS: 7681-49-4       
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                        IN THE ANALYSIS OF THE STUDY OF SODIUM FLUORIDE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Bone                          Osteosarcoma
                             Skin: Subcutaneous Tissue     Fibroma
                                                           Neurofibroma or Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                             Testes                        Adenoma
                             Thyroid Gland: Follicular Cell
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Histiocytic Sarcoma
                                                           Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Malignant Lymphoma And Histiocytic Sarcoma
                                                           Osteosarcoma
                                                           Osteosarcoma or Osteoma
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                             Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)
                                                           Squamous Cell Carcinoma
                             Skin                          Keratoacanthoma
                             Thyroid Gland: C-Cell         Adenoma
                                                           Carcinoma or Adenoma
                             Uterus                        Polyp Stromal
                                                           Sarcoma Stromal or Polyp Stromal
                             All Organs                    Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   1
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/143 (22%) 21/70 (30%)  15/70 (21%)  30/100 (30%)|  6/132 (5%)   2/69 (3%)    1/70 (1%)    5/100 (5%) |
|ADJUSTED (b)           |  52.7%        56.3%        46.2%        56.7%      |   9.5%         5.5%         2.9%         8.5%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     1/9 (11%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           | 16/41 (39%)  10/25 (40%)   7/23 (30%)  20/42 (48%) |  3/59 (5%)    1/31 (3%)    1/34 (3%)    3/54 (6%)  |
|FIRST INCIDENCE (DAYS) |   537          459 (I)      460 (I)      645       |   683          677          729 (T)      678       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.395N     P=0.387      P=0.350N     P=0.533N   |  P=0.491N     P=0.407N     P=0.208N     P=0.553N   |
|INCIDENTAL TUMOR       |  P=0.356      P=0.208      P=0.495N     P=0.286    |  P=0.555N     P=0.423N     P=0.211N     P=0.612    |
|LOGISTIC REGRESSION    |  P=0.354      P=0.213      P=0.478N     P=0.289    |  P=0.451      P=0.421N     P=0.217N     P=0.601N   |
|COCHRAN-ARMITAGE       |  P=0.200                                           |  P=0.503                                           |
|FISHER EXACT           |               P=0.149      P=0.512N     P=0.117    |               P=0.441N     P=0.235N     P=0.554    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/143 (1%)   0/70 (0%)    1/70 (1%)    0/100 (0%) |  0/132 (0%)   0/69 (0%)    1/70 (1%)    1/100 (1%) |
|ADJUSTED (b)           |   4.9%         0.0%         4.3%         0.0%      |   0.0%         0.0%         2.8%         1.7%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/41 (5%)    0/25 (0%)    1/23 (4%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          729 (T)      ---       |   ---          ---          716          719       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.222N     P=0.353N     P=0.697N     P=0.233N   |  P=0.214        (e)        P=0.388      P=0.487    |
|INCIDENTAL TUMOR       |  P=0.222N     P=0.353N     P=0.697N     P=0.233N   |  P=0.162        (e)        P=0.371      P=0.433    |
|LOGISTIC REGRESSION    |  P=0.222N     P=0.353N     P=0.697N     P=0.233N   |  P=0.197        (e)        P=0.375      P=0.473    |
|COCHRAN-ARMITAGE       |  P=0.293N                                          |  P=0.174                                           |
|FISHER EXACT           |               P=0.450N     P=0.699      P=0.345N   |                 (e)        P=0.347      P=0.431    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   2
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            | 33/143 (23%) 21/70 (30%)  16/70 (23%)  30/100 (30%)|  6/132 (5%)   2/69 (3%)    2/70 (3%)    6/100 (6%) |
|ADJUSTED (b)           |  53.5%        56.3%        49.5%        56.7%      |   9.5%         5.5%         5.6%        10.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     1/9 (11%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           | 16/41 (39%)  10/25 (40%)   8/23 (35%)  20/42 (48%) |  3/59 (5%)    1/31 (3%)    1/34 (3%)    3/54 (6%)  |
|FIRST INCIDENCE (DAYS) |   537          459 (I)      460 (I)      645       |   683          677          716          678       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.365N     P=0.434      P=0.387N     P=0.478N   |  P=0.446      P=0.407N     P=0.387N     P=0.562    |
|INCIDENTAL TUMOR       |  P=0.385      P=0.247      P=0.545N     P=0.332    |  P=0.362      P=0.423N     P=0.398N     P=0.468    |
|LOGISTIC REGRESSION    |  P=0.384      P=0.252      P=0.527N     P=0.342    |  P=0.263      P=0.421N     P=0.407N     P=0.436    |
|COCHRAN-ARMITAGE       |  P=0.218                                           |  P=0.322                                           |
|FISHER EXACT           |               P=0.178      P=0.559N     P=0.144    |               P=0.441N     P=0.434N     P=0.418    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   0/70 (0%)    1/70 (1%)    3/100 (3%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         4.3%         5.2%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    1/23 (4%)    1/42 (2%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      388       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.025 *      (e)        P=0.380      P=0.095    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.014 *      (e)        P=0.380      P=0.049 *  |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.016 *      (e)        P=0.380      P=0.067    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.015 *                                         |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.327      P=0.068    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   3
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |  1/132 (1%)   0/70 (0%)    2/70 (3%)    2/100 (2%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.8%         0.0%         4.6%         3.2%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   376          ---          568          578       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.189      P=0.636N     P=0.291      P=0.428    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.076      P=0.923N     P=0.065      P=0.246    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.159      P=0.583N     P=0.298      P=0.399    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.161                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.653N     P=0.276      P=0.397    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  9/144 (6%)   5/70 (7%)    3/67 (4%)    5/100 (5%) | 10/130 (8%)   1/68 (1%)    6/69 (9%)   12/98 (12%) |
|ADJUSTED (b)           |  16.2%        16.1%         9.0%         9.4%      |  16.9%         2.1%        15.9%        21.1%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     1/9 (11%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  4/42 (10%)   3/25 (12%)   1/23 (4%)    2/42 (5%)  |  9/58 (16%)   0/31 (0%)    4/33 (12%)  10/53 (19%) |
|FIRST INCIDENCE (DAYS) |   614          460 (I)      603          460 (I)   |   719          618          575          578       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.166N     P=0.556N     P=0.352N     P=0.247N   |  P=0.096      P=0.063N     P=0.557      P=0.316    |
|INCIDENTAL TUMOR       |  P=0.258N     P=0.586      P=0.439N     P=0.384N   |  P=0.069      P=0.071N     P=0.529      P=0.276    |
|LOGISTIC REGRESSION    |  P=0.272N     P=0.556      P=0.412N     P=0.383N   |  P=0.068      P=0.060N     P=0.511      P=0.276    |
|COCHRAN-ARMITAGE       |  P=0.313N                                          |  P=0.043 *                                         |
|FISHER EXACT           |               P=0.506      P=0.436N     P=0.453N   |               P=0.061N     P=0.501      P=0.177    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   4
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/144 (1%)   3/70 (4%)    1/67 (1%)    4/100 (4%) |  1/130 (1%)   2/68 (3%)    0/69 (0%)    1/98 (1%)  |
|ADJUSTED (b)           |   2.3%         8.4%         4.0%         7.7%      |   1.7%         5.7%         0.0%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    2/42 (5%)  |  1/58 (2%)    1/31 (3%)    0/33 (0%)    1/53 (2%)  |
|FIRST INCIDENCE (DAYS) |   537          638          718          607       |   729 (T)      702          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.336      P=0.251      P=0.727      P=0.274    |  P=0.384N     P=0.301      P=0.612N     P=0.741    |
|INCIDENTAL TUMOR       |  P=0.196      P=0.123      P=0.576      P=0.151    |  P=0.406N     P=0.293      P=0.612N     P=0.741    |
|LOGISTIC REGRESSION    |  P=0.267      P=0.206      P=0.711      P=0.206    |  P=0.397N     P=0.292      P=0.612N     P=0.741    |
|COCHRAN-ARMITAGE       |  P=0.245                                           |  P=0.446N                                          |
|FISHER EXACT           |               P=0.198      P=0.684      P=0.190    |               P=0.272      P=0.653N     P=0.676    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/144 (8%)   8/70 (11%)   4/67 (6%)    9/100 (9%) | 11/130 (8%)   3/68 (4%)    6/69 (9%)   13/98 (13%) |
|ADJUSTED (b)           |  18.1%        23.5%        12.7%        16.6%      |  18.6%         7.7%        15.9%        23.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     1/9 (11%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  4/42 (10%)   4/25 (16%)   1/23 (4%)    4/42 (10%) | 10/58 (17%)   1/31 (3%)    4/33 (12%)  11/53 (21%) |
|FIRST INCIDENCE (DAYS) |   537          460 (I)      603          460 (I)   |   719          618          575          578       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.318N     P=0.410      P=0.369N     P=0.494N   |  P=0.152      P=0.206N     P=0.581N     P=0.314    |
|INCIDENTAL TUMOR       |  P=0.518N     P=0.256      P=0.532N     P=0.467    |  P=0.111      P=0.228N     P=0.606      P=0.276    |
|LOGISTIC REGRESSION    |  P=0.478N     P=0.278      P=0.437N     P=0.508    |  P=0.110      P=0.202N     P=0.587      P=0.277    |
|COCHRAN-ARMITAGE       |  P=0.533N                                          |  P=0.071                                           |
|FISHER EXACT           |               P=0.251      P=0.452N     P=0.438    |               P=0.227N     P=0.574      P=0.170    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   5
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Ear                                                                                                                              |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   0/70 (0%)    1/70 (1%)    0/100 (0%) |  2/132 (2%)   0/70 (0%)    0/70 (0%)    1/100 (1%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.4%         0.0%      |   3.0%         0.0%         0.0%         1.5%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  1/59 (2%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          607          ---       |   647          ---          ---          647       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.547        (e)        P=0.357        (e)      |  P=0.459N     P=0.384N     P=0.370N     P=0.542N   |
|INCIDENTAL TUMOR       |  P=0.457        (e)        P=0.322        (e)      |  P=0.498N     P=0.379N     P=0.378N     P=0.588N   |
|LOGISTIC REGRESSION    |  P=0.534        (e)        P=0.354        (e)      |  P=0.490N     P=0.391N     P=0.391N     P=0.582N   |
|COCHRAN-ARMITAGE       |  P=0.532                                           |  P=0.503N                                          |
|FISHER EXACT           |                 (e)        P=0.327        (e)      |               P=0.426N     P=0.426N     P=0.603N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Ear                                                                                                                              |
|     Neurofibrosarcoma                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/144 (1%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   4.2%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   710          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.135N     P=0.365N     P=0.379N     P=0.251N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.154N     P=0.373N     P=0.405N     P=0.287N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.144N     P=0.371N     P=0.388N     P=0.270N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.166N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.452N     P=0.452N     P=0.347N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   6
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            |  3/143 (2%)   0/68 (0%)    3/70 (4%)    4/100 (4%) |  3/132 (2%)   1/70 (1%)    1/70 (1%)    0/99 (0%)  |
|ADJUSTED (b)           |   4.9%         0.0%        13.0%         8.5%      |   5.1%         3.2%         2.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    0/25 (0%)    3/23 (13%)   3/42 (7%)  |  3/59 (5%)    1/31 (3%)    1/34 (3%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   627          ---          729 (T)      614       |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.191      P=0.239N     P=0.355      P=0.454    |  P=0.089N     P=0.552N     P=0.516N     P=0.138N   |
|INCIDENTAL TUMOR       |  P=0.145      P=0.319N     P=0.334      P=0.324    |  P=0.089N     P=0.552N     P=0.516N     P=0.138N   |
|LOGISTIC REGRESSION    |  P=0.140      P=0.274N     P=0.326      P=0.361    |  P=0.089N     P=0.552N     P=0.516N     P=0.138N   |
|COCHRAN-ARMITAGE       |  P=0.112                                           |  P=0.120N                                          |
|FISHER EXACT           |               P=0.309N     P=0.309      P=0.310    |               P=0.569N     P=0.569N     P=0.185N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/143 (3%)   1/68 (1%)    4/70 (6%)    5/100 (5%) |  3/132 (2%)   1/70 (1%)    2/70 (3%)    0/99 (0%)  |
|ADJUSTED (b)           |   7.2%         4.0%        15.9%        10.4%      |   5.1%         3.2%         5.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/42 (5%)    1/25 (4%)    3/23 (13%)   3/42 (7%)  |  3/59 (5%)    1/31 (3%)    2/34 (6%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   627          729 (T)      702          614       |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.233      P=0.376N     P=0.294      P=0.450    |  P=0.135N     P=0.552N     P=0.622      P=0.138N   |
|INCIDENTAL TUMOR       |  P=0.171      P=0.458N     P=0.262      P=0.317    |  P=0.135N     P=0.552N     P=0.622      P=0.138N   |
|LOGISTIC REGRESSION    |  P=0.170      P=0.429N     P=0.260      P=0.349    |  P=0.135N     P=0.552N     P=0.622      P=0.138N   |
|COCHRAN-ARMITAGE       |  P=0.130                                           |  P=0.183N                                          |
|FISHER EXACT           |               P=0.482N     P=0.246      P=0.288    |               P=0.569N     P=0.567      P=0.185N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   7
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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 Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   1/70 (1%)    1/70 (1%)    1/100 (1%) |  2/132 (2%)   0/70 (0%)    1/70 (1%)    1/100 (1%) |
|ADJUSTED (b)           |   2.4%         2.3%         4.3%         2.4%      |   3.4%         0.0%         2.9%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    0/25 (0%)    1/23 (4%)    1/42 (2%)  |  2/59 (3%)    0/31 (0%)    1/34 (3%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      647          729 (T)      729 (T)   |   729 (T)      ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.585N     P=0.639      P=0.622      P=0.762    |  P=0.517N     P=0.389N     P=0.687N     P=0.531N   |
|INCIDENTAL TUMOR       |  P=0.597      P=0.627      P=0.622      P=0.762    |  P=0.517N     P=0.389N     P=0.687N     P=0.531N   |
|LOGISTIC REGRESSION    |  P=0.573      P=0.608      P=0.622      P=0.762    |  P=0.517N     P=0.389N     P=0.687N     P=0.531N   |
|COCHRAN-ARMITAGE       |  P=0.530                                           |  P=0.583N                                          |
|FISHER EXACT           |               P=0.548      P=0.548      P=0.653    |               P=0.426N     P=0.724N     P=0.603N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   1/70 (1%)    1/70 (1%)    1/100 (1%) |  2/132 (2%)   1/70 (1%)    0/70 (0%)    1/100 (1%) |
|ADJUSTED (b)           |   0.0%         4.0%         1.8%         1.2%      |   3.4%         3.2%         0.0%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     1/10 (10%)   1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    0/42 (0%)  |  2/59 (3%)    1/31 (3%)    0/34 (0%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      460 (I)      460 (I)   |   729 (T)      729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.408      P=0.397      P=0.521      P=0.521    |  P=0.319N     P=0.717N     P=0.366N     P=0.531N   |
|INCIDENTAL TUMOR       |  P=0.408      P=0.397      P=0.521      P=0.521    |  P=0.319N     P=0.717N     P=0.366N     P=0.531N   |
|LOGISTIC REGRESSION    |  P=0.318      P=0.397      P=0.372      P=0.417    |  P=0.319N     P=0.717N     P=0.366N     P=0.531N   |
|COCHRAN-ARMITAGE       |  P=0.323                                           |  P=0.378N                                          |
|FISHER EXACT           |               P=0.327      P=0.327      P=0.410    |               P=0.724N     P=0.426N     P=0.603N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   8
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            |  0/144 (0%)   1/70 (1%)    1/70 (1%)    1/100 (1%) |  2/132 (2%)   1/70 (1%)    1/70 (1%)    1/100 (1%) |
|ADJUSTED (b)           |   0.0%         4.0%         1.8%         1.2%      |   3.4%         3.2%         1.7%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     1/10 (10%)   1/10 (10%) |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    0/42 (0%)  |  2/59 (3%)    1/31 (3%)    0/34 (0%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      460 (I)      460 (I)   |   729 (T)      729 (T)      460 (I)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.408      P=0.397      P=0.521      P=0.521    |  P=0.399N     P=0.717N     P=0.625N     P=0.531N   |
|INCIDENTAL TUMOR       |  P=0.408      P=0.397      P=0.521      P=0.521    |  P=0.399N     P=0.717N     P=0.625N     P=0.531N   |
|LOGISTIC REGRESSION    |  P=0.318      P=0.397      P=0.372      P=0.417    |  P=0.446N     P=0.717N     P=0.718N     P=0.531N   |
|COCHRAN-ARMITAGE       |  P=0.323                                           |  P=0.462N                                          |
|FISHER EXACT           |               P=0.327      P=0.327      P=0.410    |               P=0.724N     P=0.724N     P=0.603N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |  0/132 (0%)   2/70 (3%)    1/70 (1%)    2/100 (2%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         6.5%         2.9%         3.5%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    2/31 (6%)    1/34 (3%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          729 (T)      729 (T)      716       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.316      P=0.112      P=0.390      P=0.227    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.294      P=0.112      P=0.390      P=0.194    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.308      P=0.112      P=0.390      P=0.213    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.248                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.119      P=0.347      P=0.185    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE   9
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/144 (4%)   1/70 (1%)    0/70 (0%)    2/100 (2%) | 30/132 (23%) 13/70 (19%)  15/70 (21%)  24/100 (24%)|
|ADJUSTED (b)           |  13.1%         4.0%         0.0%         4.5%      |  42.8%        34.7%        39.9%        38.1%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  4/42 (10%)   1/25 (4%)    0/23 (0%)    1/42 (2%)  | 21/59 (36%)   8/31 (26%)  12/34 (35%)  16/54 (30%) |
|FIRST INCIDENCE (DAYS) |   712          729 (T)      ---          718       |   557          618          646          613       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.100N     P=0.195N     P=0.081N     P=0.151N   |  P=0.382N     P=0.309N     P=0.383N     P=0.358N   |
|INCIDENTAL TUMOR       |  P=0.125N     P=0.197N     P=0.089N     P=0.195N   |  P=0.502      P=0.356N     P=0.457N     P=0.528N   |
|LOGISTIC REGRESSION    |  P=0.112N     P=0.195N     P=0.079N     P=0.173N   |  P=0.524N     P=0.304N     P=0.494N     P=0.482N   |
|COCHRAN-ARMITAGE       |  P=0.172N                                          |  P=0.364                                           |
|FISHER EXACT           |               P=0.271N     P=0.090N     P=0.292N   |               P=0.309N     P=0.491N     P=0.470    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/144 (4%)   1/70 (1%)    0/70 (0%)    2/100 (2%) | 30/132 (23%) 14/70 (20%)  16/70 (23%)  25/100 (25%)|
|ADJUSTED (b)           |  13.1%         4.0%         0.0%         4.5%      |  42.8%        37.6%        42.6%        39.8%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  4/42 (10%)   1/25 (4%)    0/23 (0%)    1/42 (2%)  | 21/59 (36%)   9/31 (29%)  13/34 (38%)  17/54 (31%) |
|FIRST INCIDENCE (DAYS) |   712          729 (T)      ---          718       |   557          618          646          613       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.100N     P=0.195N     P=0.081N     P=0.151N   |  P=0.428N     P=0.397N     P=0.472N     P=0.420N   |
|INCIDENTAL TUMOR       |  P=0.125N     P=0.197N     P=0.089N     P=0.195N   |  P=0.452      P=0.454N     P=0.553N     P=0.535    |
|LOGISTIC REGRESSION    |  P=0.112N     P=0.195N     P=0.079N     P=0.173N   |  P=0.476      P=0.397N     P=0.559      P=0.552N   |
|COCHRAN-ARMITAGE       |  P=0.172N                                          |  P=0.311                                           |
|FISHER EXACT           |               P=0.271N     P=0.090N     P=0.292N   |               P=0.398N     P=0.558      P=0.401    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  10
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/144 (4%)   1/70 (1%)    0/70 (0%)    2/100 (2%) | 30/132 (23%) 15/70 (21%)  16/70 (23%)  25/100 (25%)|
|ADJUSTED (b)           |  13.1%         4.0%         0.0%         4.5%      |  42.8%        40.4%        42.6%        39.8%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  4/42 (10%)   1/25 (4%)    0/23 (0%)    1/42 (2%)  | 21/59 (36%)  10/31 (32%)  13/34 (38%)  17/54 (31%) |
|FIRST INCIDENCE (DAYS) |   712          729 (T)      ---          718       |   557          618          646          613       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.100N     P=0.195N     P=0.081N     P=0.151N   |  P=0.395N     P=0.490N     P=0.472N     P=0.420N   |
|INCIDENTAL TUMOR       |  P=0.125N     P=0.197N     P=0.089N     P=0.195N   |  P=0.489      P=0.553N     P=0.553N     P=0.535    |
|LOGISTIC REGRESSION    |  P=0.112N     P=0.195N     P=0.079N     P=0.173N   |  P=0.511      P=0.494N     P=0.559      P=0.552N   |
|COCHRAN-ARMITAGE       |  P=0.172N                                          |  P=0.339                                           |
|FISHER EXACT           |               P=0.271N     P=0.090N     P=0.292N   |               P=0.491N     P=0.558      P=0.401    |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   1/70 (1%)    1/70 (1%)    2/100 (2%) |  0/132 (0%)   1/70 (1%)    1/70 (1%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         4.0%         3.2%         4.5%      |   0.0%         3.2%         2.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    1/42 (2%)  |  0/59 (0%)    1/31 (3%)    1/34 (3%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      698          711       |   ---          729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.186      P=0.397      P=0.389      P=0.229    |  P=0.536N     P=0.372      P=0.390        (e)      |
|INCIDENTAL TUMOR       |  P=0.149      P=0.397      P=0.337      P=0.193    |  P=0.536N     P=0.372      P=0.390        (e)      |
|LOGISTIC REGRESSION    |  P=0.161      P=0.397      P=0.360      P=0.207    |  P=0.536N     P=0.372      P=0.390        (e)      |
|COCHRAN-ARMITAGE       |  P=0.127                                           |  P=0.583N                                          |
|FISHER EXACT           |               P=0.327      P=0.327      P=0.167    |               P=0.347      P=0.347        (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  11
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   0/70 (0%)    1/70 (1%)    1/100 (1%) |  1/132 (1%)   0/70 (0%)    0/70 (0%)    3/100 (3%) |
|ADJUSTED (b)           |   1.2%         0.0%         2.9%         1.5%      |   1.4%         0.0%         0.0%         4.5%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   634          ---          681          620       |   674          ---          ---          628       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.436      P=0.615N     P=0.611      P=0.711    |  P=0.099      P=0.613N     P=0.633N     P=0.259    |
|INCIDENTAL TUMOR       |  P=0.301      P=0.791N     P=0.559      P=0.522    |  P=0.048 *    P=0.612N     P=0.629N     P=0.139    |
|LOGISTIC REGRESSION    |  P=0.407      P=0.642N     P=0.589      P=0.684    |  P=0.083      P=0.631N     P=0.631N     P=0.224    |
|COCHRAN-ARMITAGE       |  P=0.398                                           |  P=0.077                                           |
|FISHER EXACT           |               P=0.673N     P=0.548      P=0.653    |               P=0.653N     P=0.653N     P=0.215    |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   1/70 (1%)    2/70 (3%)    3/100 (3%) |  1/132 (1%)   1/70 (1%)    1/70 (1%)    3/100 (3%) |
|ADJUSTED (b)           |   1.2%         4.0%         6.0%         5.9%      |   1.4%         3.2%         2.9%         4.5%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    1/42 (2%)  |  0/59 (0%)    1/31 (3%)    1/34 (3%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   634          729 (T)      681          620       |   674          729 (T)      729 (T)      628       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.165      P=0.634      P=0.294      P=0.262    |  P=0.185      P=0.620      P=0.619      P=0.259    |
|INCIDENTAL TUMOR       |  P=0.090      P=0.537      P=0.224      P=0.124    |  P=0.118      P=0.621      P=0.622      P=0.139    |
|LOGISTIC REGRESSION    |  P=0.128      P=0.605      P=0.257      P=0.211    |  P=0.157      P=0.611      P=0.611      P=0.224    |
|COCHRAN-ARMITAGE       |  P=0.109                                           |  P=0.141                                           |
|FISHER EXACT           |               P=0.548      P=0.250      P=0.189    |               P=0.574      P=0.574      P=0.215    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  12
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Mucosa                                                                                                                      |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   0/70 (0%)    1/70 (1%)    1/100 (1%) |  1/132 (1%)   0/70 (0%)    0/70 (0%)    2/100 (2%) |
|ADJUSTED (b)           |   1.2%         0.0%         2.9%         1.5%      |   1.4%         0.0%         0.0%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   634          ---          681          620       |   674          ---          ---          628       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.436      P=0.615N     P=0.611      P=0.711    |  P=0.244      P=0.613N     P=0.633N     P=0.455    |
|INCIDENTAL TUMOR       |  P=0.301      P=0.791N     P=0.559      P=0.522    |  P=0.168      P=0.612N     P=0.629N     P=0.339    |
|LOGISTIC REGRESSION    |  P=0.407      P=0.642N     P=0.589      P=0.684    |  P=0.221      P=0.631N     P=0.631N     P=0.418    |
|COCHRAN-ARMITAGE       |  P=0.398                                           |  P=0.210                                           |
|FISHER EXACT           |               P=0.673N     P=0.548      P=0.653    |               P=0.653N     P=0.653N     P=0.397    |
|=================================================================================================================================|
|                                                                                                                                 |
|Parathyroid Gland                                                                                                                |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/139 (3%)   1/70 (1%)    1/69 (1%)    1/97 (1%)  |  0/131 (0%)   0/66 (0%)    1/66 (2%)    1/99 (1%)  |
|ADJUSTED (b)           |   9.3%         4.0%         4.3%         2.3%      |   0.0%         0.0%         2.4%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  3/41 (7%)    1/25 (4%)    1/23 (4%)    0/39 (0%)  |  0/58 (0%)    0/29 (0%)    0/32 (0%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |   719          729 (T)      729 (T)      726       |   ---          ---          662          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.154N     P=0.362N     P=0.398N     P=0.196N   |  P=0.204        (e)        P=0.377      P=0.486    |
|INCIDENTAL TUMOR       |  P=0.180N     P=0.364N     P=0.405N     P=0.243N   |  P=0.192        (e)        P=0.371      P=0.486    |
|LOGISTIC REGRESSION    |  P=0.176N     P=0.368N     P=0.396N     P=0.219N   |  P=0.191        (e)        P=0.358      P=0.486    |
|COCHRAN-ARMITAGE       |  P=0.228N                                          |  P=0.175                                           |
|FISHER EXACT           |               P=0.456N     P=0.462N     P=0.316N   |                 (e)        P=0.335      P=0.430    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  13
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            | 19/143 (13%)  9/69 (13%)   9/69 (13%)  15/100 (15%)| 39/132 (30%) 24/70 (34%)  22/70 (31%)  32/100 (32%)|
|ADJUSTED (b)           |  32.5%        26.7%        29.8%        25.2%      |  54.3%        55.0%        54.9%        48.6%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/9 (11%)    0/9 (0%)     0/10 (0%)    2/10 (20%) |  0/10 (0%)    3/10 (30%)   2/10 (20%)   1/9 (11%)  |
|TERMINAL (d)           | 10/42 (24%)   3/25 (12%)   4/22 (18%)   5/42 (12%) | 28/59 (47%)  13/31 (42%)  17/34 (50%)  21/54 (39%) |
|FIRST INCIDENCE (DAYS) |   417          623          404          460 (I)   |   402          459 (I)      460 (I)      459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.402N     P=0.373N     P=0.467N     P=0.389N   |  P=0.254N     P=0.355      P=0.523N     P=0.361N   |
|INCIDENTAL TUMOR       |  P=0.391      P=0.536N     P=0.558      P=0.495    |  P=0.451N     P=0.236      P=0.426      P=0.539    |
|LOGISTIC REGRESSION    |  P=0.437      P=0.522N     P=0.582      P=0.483    |  P=0.471N     P=0.247      P=0.409      P=0.554N   |
|COCHRAN-ARMITAGE       |  P=0.381                                           |  P=0.435                                           |
|FISHER EXACT           |               P=0.574N     P=0.574N     P=0.421    |               P=0.296      P=0.451      P=0.397    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/143 (0%)   0/69 (0%)    1/69 (1%)    0/100 (0%) |  0/132 (0%)   0/70 (0%)    2/70 (3%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         4.5%         0.0%      |   0.0%         0.0%         5.1%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    1/22 (5%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    1/34 (3%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      ---       |   ---          ---          647          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.580        (e)        P=0.371        (e)      |  P=0.456        (e)        P=0.128        (e)      |
|INCIDENTAL TUMOR       |  P=0.580        (e)        P=0.371        (e)      |  P=0.432        (e)        P=0.121        (e)      |
|LOGISTIC REGRESSION    |  P=0.580        (e)        P=0.371        (e)      |  P=0.432        (e)        P=0.110        (e)      |
|COCHRAN-ARMITAGE       |  P=0.533                                           |  P=0.417                                           |
|FISHER EXACT           |                 (e)        P=0.325        (e)      |                 (e)        P=0.119        (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  14
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 19/143 (13%)  9/69 (13%)   9/69 (13%)  15/100 (15%)| 39/132 (30%) 24/70 (34%)  24/70 (34%)  32/100 (32%)|
|ADJUSTED (b)           |  32.5%        26.7%        29.8%        25.2%      |  54.3%        55.0%        58.5%        48.6%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/9 (11%)    0/9 (0%)     0/10 (0%)    2/10 (20%) |  0/10 (0%)    3/10 (30%)   2/10 (20%)   1/9 (11%)  |
|TERMINAL (d)           | 10/42 (24%)   3/25 (12%)   4/22 (18%)   5/42 (12%) | 28/59 (47%)  13/31 (42%)  18/34 (53%)  21/54 (39%) |
|FIRST INCIDENCE (DAYS) |   417          623          404          460 (I)   |   402          459 (I)      460 (I)      459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.402N     P=0.373N     P=0.467N     P=0.389N   |  P=0.280N     P=0.355      P=0.442      P=0.361N   |
|INCIDENTAL TUMOR       |  P=0.391      P=0.536N     P=0.558      P=0.495    |  P=0.486N     P=0.236      P=0.261      P=0.539    |
|LOGISTIC REGRESSION    |  P=0.437      P=0.522N     P=0.582      P=0.483    |  P=0.508N     P=0.247      P=0.247      P=0.554N   |
|COCHRAN-ARMITAGE       |  P=0.381                                           |  P=0.400                                           |
|FISHER EXACT           |               P=0.574N     P=0.574N     P=0.421    |               P=0.296      P=0.296      P=0.397    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/144 (8%)   2/70 (3%)    2/70 (3%)    8/100 (8%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    3/100 (3%) |
|ADJUSTED (b)           |  19.9%         8.0%         6.1%        16.8%      |   0.0%         0.0%         0.0%         5.4%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  6/42 (14%)   2/25 (8%)    1/23 (4%)    5/42 (12%) |  0/59 (0%)    0/31 (0%)    0/34 (0%)    2/54 (4%)  |
|FIRST INCIDENCE (DAYS) |   549          729 (T)      460 (I)      661       |   ---          ---          ---          719       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.430N     P=0.091N     P=0.095N     P=0.385N   |  P=0.022 *      (e)          (e)        P=0.109    |
|INCIDENTAL TUMOR       |  P=0.522N     P=0.121N     P=0.112N     P=0.522N   |  P=0.018 *      (e)          (e)        P=0.095    |
|LOGISTIC REGRESSION    |  P=0.521      P=0.115N     P=0.143N     P=0.529N   |  P=0.020 *      (e)          (e)        P=0.106    |
|COCHRAN-ARMITAGE       |  P=0.452                                           |  P=0.014 *                                         |
|FISHER EXACT           |               P=0.141N     P=0.141N     P=0.550    |                 (e)          (e)        P=0.079    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  15
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                                             |
|     Papilloma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   1/70 (1%)    0/70 (0%)    2/100 (2%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         2.9%         0.0%         4.4%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    1/42 (2%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          691          ---          710       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.191      P=0.390        (e)        P=0.229    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.151      P=0.373        (e)        P=0.193    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.171      P=0.369        (e)        P=0.206    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.144                                           |    (e)                                             |
|FISHER EXACT           |               P=0.327        (e)        P=0.167    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   3/70 (4%)    1/70 (1%)    4/100 (4%) |  1/132 (1%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   2.4%        10.7%         4.3%         9.1%      |   1.2%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    2/25 (8%)    1/23 (4%)    3/42 (7%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      691          729 (T)      710       |   643          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.254      P=0.144      P=0.622      P=0.176    |  P=0.311N     P=0.631N     P=0.618N     P=0.537N   |
|INCIDENTAL TUMOR       |  P=0.228      P=0.139      P=0.622      P=0.156    |  P=0.393N     P=0.729N     P=0.764N     P=0.649N   |
|LOGISTIC REGRESSION    |  P=0.218      P=0.131      P=0.622      P=0.151    |  P=0.322N     P=0.630N     P=0.630N     P=0.553N   |
|COCHRAN-ARMITAGE       |  P=0.150                                           |  P=0.324N                                          |
|FISHER EXACT           |               P=0.104      P=0.548      P=0.093    |               P=0.653N     P=0.653N     P=0.569N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  16
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   2/70 (3%)    1/70 (1%)    2/100 (2%) |  1/132 (1%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   2.4%         8.0%         4.3%         4.8%      |   1.2%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    2/25 (8%)    1/23 (4%)    2/42 (5%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   643          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.510      P=0.322      P=0.622      P=0.500    |  P=0.311N     P=0.631N     P=0.618N     P=0.537N   |
|INCIDENTAL TUMOR       |  P=0.510      P=0.322      P=0.622      P=0.500    |  P=0.393N     P=0.729N     P=0.764N     P=0.649N   |
|LOGISTIC REGRESSION    |  P=0.510      P=0.322      P=0.622      P=0.500    |  P=0.322N     P=0.630N     P=0.630N     P=0.553N   |
|COCHRAN-ARMITAGE       |  P=0.383                                           |  P=0.324N                                          |
|FISHER EXACT           |               P=0.250      P=0.548      P=0.366    |               P=0.653N     P=0.653N     P=0.569N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   0/70 (0%)    2/70 (3%)    0/100 (0%) |  1/132 (1%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   2.4%         0.0%         8.7%         0.0%      |   1.3%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    0/25 (0%)    2/23 (9%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          729 (T)      ---       |   647          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.512N     P=0.603N     P=0.295      P=0.500N   |  P=0.307N     P=0.619N     P=0.614N     P=0.527N   |
|INCIDENTAL TUMOR       |  P=0.512N     P=0.603N     P=0.295      P=0.500N   |  P=0.334N     P=0.612N     P=0.629N     P=0.567N   |
|LOGISTIC REGRESSION    |  P=0.512N     P=0.603N     P=0.295      P=0.500N   |  P=0.322N     P=0.631N     P=0.631N     P=0.552N   |
|COCHRAN-ARMITAGE       |  P=0.602N                                          |  P=0.324N                                          |
|FISHER EXACT           |               P=0.673N     P=0.250      P=0.590N   |               P=0.653N     P=0.653N     P=0.569N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  17
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/144 (9%)   5/70 (7%)    5/70 (7%)   12/100 (12%)|  2/132 (2%)   0/70 (0%)    0/70 (0%)    3/100 (3%) |
|ADJUSTED (b)           |  24.4%        18.5%        18.9%        25.1%      |   2.5%         0.0%         0.0%         5.4%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  8/42 (19%)   4/25 (16%)   4/23 (17%)   8/42 (19%) |  0/59 (0%)    0/31 (0%)    0/34 (0%)    2/54 (4%)  |
|FIRST INCIDENCE (DAYS) |   549          691          460 (I)      661       |   643          ---          ---          719       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.487      P=0.285N     P=0.306N     P=0.569N   |  P=0.253      P=0.385N     P=0.374N     P=0.450    |
|INCIDENTAL TUMOR       |  P=0.393      P=0.347N     P=0.341N     P=0.462    |  P=0.192      P=0.436N     P=0.467N     P=0.360    |
|LOGISTIC REGRESSION    |  P=0.327      P=0.346N     P=0.414N     P=0.434    |  P=0.222      P=0.391N     P=0.391N     P=0.405    |
|COCHRAN-ARMITAGE       |  P=0.235                                           |  P=0.201                                           |
|FISHER EXACT           |               P=0.429N     P=0.429N     P=0.293    |               P=0.426N     P=0.426N     P=0.371    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   2/70 (3%)    3/70 (4%)    4/100 (4%) |  0/132 (0%)   1/70 (1%)    0/70 (0%)    1/100 (1%) |
|ADJUSTED (b)           |   0.0%         6.0%        10.0%         7.8%      |   0.0%         2.7%         0.0%         1.2%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    2/42 (5%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          584          668          587       |   ---          709          ---          460 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.063      P=0.126      P=0.038 *    P=0.055    |  P=0.450      P=0.388        (e)        P=0.479    |
|INCIDENTAL TUMOR       |  P=0.028 *    P=0.065      P=0.021 *    P=0.028 *  |  P=0.412      P=0.388        (e)        P=0.479    |
|LOGISTIC REGRESSION    |  P=0.040 *    P=0.103      P=0.031 *    P=0.035 *  |  P=0.415      P=0.373        (e)        P=0.443    |
|COCHRAN-ARMITAGE       |  P=0.032 *                                         |  P=0.417                                           |
|FISHER EXACT           |               P=0.106      P=0.034 *    P=0.027 *  |               P=0.347        (e)        P=0.431    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  18
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                        |
|     Neurofibroma or Fibroma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   3/70 (4%)    4/70 (6%)    4/100 (4%) |  0/132 (0%)   1/70 (1%)    0/70 (0%)    1/100 (1%) |
|ADJUSTED (b)           |   0.0%         9.9%        13.6%         7.8%      |   0.0%         2.7%         0.0%         1.2%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |
|TERMINAL (d)           |  0/42 (0%)    2/25 (8%)    0/23 (0%)    2/42 (5%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          584          668          587       |   ---          709          ---          460 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.103      P=0.045 *    P=0.013 *    P=0.055    |  P=0.450      P=0.388        (e)        P=0.479    |
|INCIDENTAL TUMOR       |  P=0.049 *    P=0.022 *    P=0.005 **   P=0.028 *  |  P=0.412      P=0.388        (e)        P=0.479    |
|LOGISTIC REGRESSION    |  P=0.066      P=0.033 *    P=0.010 **   P=0.035 *  |  P=0.415      P=0.373        (e)        P=0.443    |
|COCHRAN-ARMITAGE       |  P=0.052                                           |  P=0.417                                           |
|FISHER EXACT           |               P=0.034 *    P=0.011 *    P=0.027 *  |               P=0.347        (e)        P=0.431    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   2/70 (3%)    0/70 (0%)    0/100 (0%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         6.4%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          699          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.275N     P=0.130        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.335N     P=0.113        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.292N     P=0.116        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.315N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.106        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  19
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   5/70 (7%)    5/70 (7%)    4/100 (4%) |  0/132 (0%)   1/70 (1%)    1/70 (1%)    2/100 (2%) |
|ADJUSTED (b)           |   1.4%        15.6%        15.9%         7.8%      |   0.0%         2.7%         2.4%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |
|TERMINAL (d)           |  0/42 (0%)    2/25 (8%)    0/23 (0%)    2/42 (5%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   646          584          648          587       |   ---          709          662          460 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.282      P=0.025 *    P=0.018 *    P=0.154    |  P=0.173      P=0.388      P=0.377      P=0.225    |
|INCIDENTAL TUMOR       |  P=0.150      P=0.012 *    P=0.006 **   P=0.089    |  P=0.125      P=0.388      P=0.371      P=0.192    |
|LOGISTIC REGRESSION    |  P=0.205      P=0.015 *    P=0.006 **   P=0.107    |  P=0.144      P=0.373      P=0.369      P=0.178    |
|COCHRAN-ARMITAGE       |  P=0.170                                           |  P=0.141                                           |
|FISHER EXACT           |               P=0.015 *    P=0.015 *    P=0.093    |               P=0.347      P=0.347      P=0.185    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   2/70 (3%)    1/70 (1%)    0/100 (0%) |  0/132 (0%)   0/70 (0%)    1/70 (1%)    1/100 (1%) |
|ADJUSTED (b)           |   1.4%         6.4%         2.6%         0.0%      |   0.0%         0.0%         2.4%         1.6%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   646          699          648          ---       |   ---          ---          662          716       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.232N     P=0.316      P=0.607      P=0.532N   |  P=0.205        (e)        P=0.377      P=0.494    |
|INCIDENTAL TUMOR       |  P=0.302N     P=0.284      P=0.569      P=0.587N   |  P=0.157        (e)        P=0.371      P=0.433    |
|LOGISTIC REGRESSION    |  P=0.259N     P=0.277      P=0.589      P=0.565N   |  P=0.185        (e)        P=0.369      P=0.470    |
|COCHRAN-ARMITAGE       |  P=0.275N                                          |  P=0.173                                           |
|FISHER EXACT           |               P=0.250      P=0.548      P=0.590N   |                 (e)        P=0.347      P=0.431    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  20
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |107/144 (74%) 52/70 (74%)  52/70 (74%)  77/100 (77%)|                                                    |
|ADJUSTED (b)           | 100.0%       100.0%        98.1%        98.7%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |                                                    |
|INTERIM SACRIFICE 2 (c)|  2/9 (22%)    6/9 (67%)    6/10 (60%)   4/10 (40%) |                                                    |
|TERMINAL (d)           | 42/42 (100%) 25/25 (100%) 22/23 (96%)  41/42 (98%) |                                                    |
|FIRST INCIDENCE (DAYS) |   414          459 (I)      459 (I)      459 (I)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.030N*    P=0.088N     P=0.211N     P=0.022N*  |                                                    |
|INCIDENTAL TUMOR       |  P=0.507      P=0.513      P=0.297      P=0.489    |                                                    |
|LOGISTIC REGRESSION    |  P=0.405      P=0.503      P=0.197      P=0.586    |                                                    |
|COCHRAN-ARMITAGE       |  P=0.342                                           |                                                    |
|FISHER EXACT           |               P=0.561N     P=0.561N     P=0.373    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 21/144 (15%) 10/70 (14%)  10/70 (14%)  13/100 (13%)| 20/132 (15%)  4/70 (6%)    7/70 (10%)  13/100 (13%)|
|ADJUSTED (b)           |  35.0%        33.1%        28.9%        23.7%      |  28.0%         9.9%        17.4%        22.9%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     1/10 (10%)   1/10 (10%) |  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  9/42 (21%)   6/25 (24%)   3/23 (13%)   6/42 (14%) | 11/59 (19%)   2/31 (6%)    3/34 (9%)   11/54 (20%) |
|FIRST INCIDENCE (DAYS) |   571          669          459 (I)      459 (I)   |   515          459 (I)      646          714       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.159N     P=0.366N     P=0.438N     P=0.159N   |  P=0.314N     P=0.040N*    P=0.181N     P=0.207N   |
|INCIDENTAL TUMOR       |  P=0.318N     P=0.474N     P=0.548N     P=0.354N   |  P=0.470N     P=0.058N     P=0.270N     P=0.340N   |
|LOGISTIC REGRESSION    |  P=0.300N     P=0.457N     P=0.562N     P=0.321N   |  P=0.421N     P=0.043N*    P=0.218N     P=0.276N   |
|COCHRAN-ARMITAGE       |  P=0.397N                                          |  P=0.507N                                          |
|FISHER EXACT           |               P=0.566N     P=0.566N     P=0.438N   |               P=0.036N*    P=0.212N     P=0.394N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  21
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   1/70 (1%)    0/70 (0%)    4/100 (4%) |  1/132 (1%)   0/70 (0%)    1/70 (1%)    1/100 (1%) |
|ADJUSTED (b)           |   2.2%         1.7%         0.0%         9.1%      |   1.7%         0.0%         2.9%         1.9%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    3/42 (7%)  |  1/59 (2%)    0/31 (0%)    1/34 (3%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |   719          424          ---          710       |   729 (T)      ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.099      P=0.611      P=0.638N     P=0.175    |  P=0.475      P=0.628N     P=0.634      P=0.742    |
|INCIDENTAL TUMOR       |  P=0.059      P=0.480      P=0.663N     P=0.134    |  P=0.475      P=0.628N     P=0.634      P=0.742    |
|LOGISTIC REGRESSION    |  P=0.066      P=0.593      P=0.629N     P=0.146    |  P=0.475      P=0.628N     P=0.634      P=0.742    |
|COCHRAN-ARMITAGE       |  P=0.057                                           |  P=0.418                                           |
|FISHER EXACT           |               P=0.548      P=0.673N     P=0.093    |               P=0.653N     P=0.574      P=0.677    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 22/144 (15%) 11/70 (16%)  10/70 (14%)  17/100 (17%)| 21/132 (16%)  4/70 (6%)    8/70 (11%)  14/100 (14%)|
|ADJUSTED (b)           |  36.4%        34.2%        28.9%        31.5%      |  29.5%         9.9%        20.1%        24.7%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     1/10 (10%)   1/10 (10%) |  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  9/42 (21%)   6/25 (24%)   3/23 (13%)   9/42 (21%) | 12/59 (20%)   2/31 (6%)    4/34 (12%)  12/54 (22%) |
|FIRST INCIDENCE (DAYS) |   571          424          459 (I)      459 (I)   |   515          459 (I)      646          714       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.324N     P=0.416N     P=0.389N     P=0.336N   |  P=0.353N     P=0.030N*    P=0.219N     P=0.217N   |
|INCIDENTAL TUMOR       |  P=0.489      P=0.563N     P=0.496N     P=0.537    |  P=0.510N     P=0.044N*    P=0.318N     P=0.350N   |
|LOGISTIC REGRESSION    |  P=0.518      P=0.533N     P=0.505N     P=0.569    |  P=0.468N     P=0.032N*    P=0.266N     P=0.288N   |
|COCHRAN-ARMITAGE       |  P=0.415                                           |  P=0.503                                           |
|FISHER EXACT           |               P=0.541      P=0.512N     P=0.425    |               P=0.027N*    P=0.260N     P=0.416N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  22
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            |  0/144 (0%)   0/70 (0%)    1/70 (1%)    3/100 (3%) |  0/132 (0%)   0/70 (0%)    1/70 (1%)    1/100 (1%) |
|ADJUSTED (b)           |   0.0%         0.0%         4.3%         7.1%      |   0.0%         0.0%         2.9%         1.6%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    1/23 (4%)    3/42 (7%)  |  0/59 (0%)    0/31 (0%)    1/34 (3%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      729 (T)   |   ---          ---          729 (T)      716       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.030 *      (e)        P=0.380      P=0.121    |  P=0.213        (e)        P=0.390      P=0.494    |
|INCIDENTAL TUMOR       |  P=0.030 *      (e)        P=0.380      P=0.121    |  P=0.184        (e)        P=0.390      P=0.433    |
|LOGISTIC REGRESSION    |  P=0.030 *      (e)        P=0.380      P=0.121    |  P=0.200        (e)        P=0.390      P=0.470    |
|COCHRAN-ARMITAGE       |  P=0.015 *                                         |  P=0.173                                           |
|FISHER EXACT           |                 (e)        P=0.327      P=0.068    |                 (e)        P=0.347      P=0.431    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   1/70 (1%)    0/70 (0%)    2/100 (2%) |  2/132 (2%)   0/70 (0%)    2/70 (3%)    1/100 (1%) |
|ADJUSTED (b)           |   1.9%         4.0%         0.0%         3.5%      |   3.4%         0.0%         5.9%         1.4%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    1/42 (2%)  |  2/59 (3%)    0/31 (0%)    2/34 (6%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   712          729 (T)      ---          459 (I)   |   729 (T)      ---          729 (T)      646       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.423      P=0.629      P=0.616N     P=0.498    |  P=0.577N     P=0.389N     P=0.484      P=0.538N   |
|INCIDENTAL TUMOR       |  P=0.395      P=0.627      P=0.663N     P=0.463    |  P=0.590      P=0.389N     P=0.484      P=0.559N   |
|LOGISTIC REGRESSION    |  P=0.342      P=0.630      P=0.634N     P=0.384    |  P=0.577      P=0.389N     P=0.484      P=0.568N   |
|COCHRAN-ARMITAGE       |  P=0.328                                           |  P=0.538                                           |
|FISHER EXACT           |               P=0.548      P=0.673N     P=0.366    |               P=0.426N     P=0.431      P=0.603N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  23
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   1/70 (1%)    1/70 (1%)    5/100 (5%) |  2/132 (2%)   0/70 (0%)    3/70 (4%)    2/100 (2%) |
|ADJUSTED (b)           |   1.9%         4.0%         4.3%        10.6%      |   3.4%         0.0%         8.8%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    1/23 (4%)    4/42 (10%) |  2/59 (3%)    0/31 (0%)    3/34 (9%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   712          729 (T)      729 (T)      459 (I)   |   729 (T)      ---          729 (T)      646       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.048 *    P=0.629      P=0.623      P=0.107    |  P=0.344      P=0.389N     P=0.262      P=0.660    |
|INCIDENTAL TUMOR       |  P=0.043 *    P=0.627      P=0.595      P=0.095    |  P=0.313      P=0.389N     P=0.262      P=0.616    |
|LOGISTIC REGRESSION    |  P=0.027 *    P=0.630      P=0.613      P=0.055    |  P=0.312      P=0.389N     P=0.262      P=0.626    |
|COCHRAN-ARMITAGE       |  P=0.020 *                                         |  P=0.266                                           |
|FISHER EXACT           |               P=0.548      P=0.548      P=0.044 *  |               P=0.426N     P=0.227      P=0.579    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/132 (0%)   1/70 (1%)    0/70 (0%)    2/100 (2%) |
|ADJUSTED (b)           |                                                    |   0.0%         2.3%         0.0%         3.7%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |                                                    |  0/59 (0%)    0/31 (0%)    0/34 (0%)    2/54 (4%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          659          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.191      P=0.384        (e)        P=0.219    |
|INCIDENTAL TUMOR       |                                                    |  P=0.179      P=0.388        (e)        P=0.219    |
|LOGISTIC REGRESSION    |                                                    |  P=0.176      P=0.369        (e)        P=0.219    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.157                                           |
|FISHER EXACT           |                                                    |               P=0.347        (e)        P=0.185    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  24
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 13/132 (10%)  4/70 (6%)    7/70 (10%)   2/100 (2%) |
|ADJUSTED (b)           |                                                    |  18.4%        11.6%        16.3%         3.2%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |                                                    |  8/59 (14%)   3/31 (10%)   3/34 (9%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   376          620          460 (I)      631       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.018N*    P=0.236N     P=0.541N     P=0.008N** |
|INCIDENTAL TUMOR       |                                                    |  P=0.044N*    P=0.327N     P=0.489      P=0.020N*  |
|LOGISTIC REGRESSION    |                                                    |  P=0.029N*    P=0.241N     P=0.565      P=0.013N*  |
|COCHRAN-ARMITAGE       |                                                    |  P=0.035N*                                         |
|FISHER EXACT           |                                                    |               P=0.233N     P=0.576      P=0.013N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 13/132 (10%)  4/70 (6%)    7/70 (10%)   3/100 (3%) |
|ADJUSTED (b)           |                                                    |  18.4%        11.6%        16.3%         4.3%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |                                                    |  8/59 (14%)   3/31 (10%)   3/34 (9%)    1/54 (2%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   376          620          460 (I)      338       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.039N*    P=0.236N     P=0.541N     P=0.022N*  |
|INCIDENTAL TUMOR       |                                                    |  P=0.097N     P=0.327N     P=0.489      P=0.055N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.060N     P=0.241N     P=0.565      P=0.035N*  |
|COCHRAN-ARMITAGE       |                                                    |  P=0.067N                                          |
|FISHER EXACT           |                                                    |               P=0.233N     P=0.576      P=0.034N*  |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  25
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/144 (3%)   1/70 (1%)    1/70 (1%)    3/100 (3%) |  1/132 (1%)   0/70 (0%)    1/70 (1%)    1/100 (1%) |
|ADJUSTED (b)           |   5.6%         3.2%         2.6%         4.6%      |   1.1%         0.0%         2.9%         1.4%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    1/34 (3%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   533          706          648          570       |   620          ---          729 (T)      613       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.564N     P=0.404N     P=0.442N     P=0.612N   |  P=0.449      P=0.636N     P=0.617      P=0.711    |
|INCIDENTAL TUMOR       |  P=0.357      P=0.563N     P=0.585N     P=0.410    |  P=0.354      P=0.729N     P=0.547      P=0.587    |
|LOGISTIC REGRESSION    |  P=0.409      P=0.439N     P=0.455N     P=0.483    |  P=0.426      P=0.629N     P=0.608      P=0.698    |
|COCHRAN-ARMITAGE       |  P=0.505                                           |  P=0.418                                           |
|FISHER EXACT           |               P=0.472N     P=0.472N     P=0.603    |               P=0.653N     P=0.574      P=0.677    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/144 (1%)   0/70 (0%)    0/70 (0%)    2/100 (2%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    1/100 (1%) |
|ADJUSTED (b)           |   2.0%         0.0%         0.0%         2.7%      |   0.0%         0.0%         0.0%         1.5%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   716          ---          ---          282       |   ---          ---          ---          678       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.225      P=0.620N     P=0.627N     P=0.426    |  P=0.201        (e)          (e)        P=0.482    |
|INCIDENTAL TUMOR       |  P=0.106      P=0.627N     P=0.663N     P=0.229    |  P=0.167        (e)          (e)        P=0.433    |
|LOGISTIC REGRESSION    |  P=0.191      P=0.617N     P=0.631N     P=0.367    |  P=0.185        (e)          (e)        P=0.453    |
|COCHRAN-ARMITAGE       |  P=0.195                                           |  P=0.178                                           |
|FISHER EXACT           |               P=0.673N     P=0.673N     P=0.366    |                 (e)          (e)        P=0.431    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  26
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            |  0/144 (0%)   3/70 (4%)    1/70 (1%)    1/100 (1%) |  0/132 (0%)   0/70 (0%)    1/70 (1%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%        10.5%         3.4%         1.5%      |   0.0%         0.0%         2.5%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          706          715          614       |   ---          ---          663          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.527N     P=0.046 *    P=0.387      P=0.457    |  P=0.560        (e)        P=0.372        (e)      |
|INCIDENTAL TUMOR       |  P=0.540      P=0.041 *    P=0.337      P=0.299    |  P=0.532        (e)        P=0.371        (e)      |
|LOGISTIC REGRESSION    |  P=0.576N     P=0.041 *    P=0.368      P=0.430    |  P=0.550        (e)        P=0.369        (e)      |
|COCHRAN-ARMITAGE       |  P=0.572                                           |  P=0.544                                           |
|FISHER EXACT           |               P=0.034 *    P=0.327      P=0.410    |                 (e)        P=0.347        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 71/144 (49%) 23/70 (33%)  21/70 (30%)  47/100 (47%)| 33/132 (25%) 16/70 (23%)  14/70 (20%)  20/100 (20%)|
|ADJUSTED (b)           |  80.7%        55.6%        49.8%        69.1%      |  40.9%        36.7%        35.9%        29.7%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  3/9 (33%)    0/9 (0%)     3/10 (30%)   0/10 (0%)  |  0/10 (0%)    1/10 (10%)   0/10 (0%)    2/9 (22%)  |
|TERMINAL (d)           | 27/42 (64%)   9/25 (36%)   6/23 (26%)  22/42 (52%) | 15/59 (25%)   6/31 (19%)  10/34 (29%)  11/54 (20%) |
|FIRST INCIDENCE (DAYS) |   325          422          459 (I)      389       |   379          451          571          338       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.081N     P=0.005N**   P=0.003N**   P=0.038N*  |  P=0.071N     P=0.410N     P=0.226N     P=0.097N   |
|INCIDENTAL TUMOR       |  P=0.522      P=0.026N*    P=0.007N**   P=0.423N   |  P=0.234N     P=0.536      P=0.435N     P=0.272N   |
|LOGISTIC REGRESSION    |  P=0.410N     P=0.007N**   P=0.005N**   P=0.238N   |  P=0.136N     P=0.472N     P=0.289N     P=0.184N   |
|COCHRAN-ARMITAGE       |  P=0.423N                                          |  P=0.186N                                          |
|FISHER EXACT           |               P=0.016N*    P=0.005N**   P=0.411N   |               P=0.438N     P=0.268N     P=0.230N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  27
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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 And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   3/70 (4%)    1/70 (1%)    1/100 (1%) |  0/132 (0%)   0/70 (0%)    1/70 (1%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%        10.5%         3.4%         1.5%      |   0.0%         0.0%         2.5%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/25 (4%)    0/23 (0%)    0/42 (0%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          706          715          614       |   ---          ---          663          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.527N     P=0.046 *    P=0.387      P=0.457    |  P=0.560        (e)        P=0.372        (e)      |
|INCIDENTAL TUMOR       |  P=0.540      P=0.041 *    P=0.337      P=0.299    |  P=0.532        (e)        P=0.371        (e)      |
|LOGISTIC REGRESSION    |  P=0.576N     P=0.041 *    P=0.368      P=0.430    |  P=0.550        (e)        P=0.369        (e)      |
|COCHRAN-ARMITAGE       |  P=0.572                                           |  P=0.544                                           |
|FISHER EXACT           |               P=0.034 *    P=0.327      P=0.410    |                 (e)        P=0.347        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/144 (3%)   1/70 (1%)    1/70 (1%)    2/100 (2%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   5.4%         3.7%         2.1%         3.8%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    0/25 (0%)    0/23 (0%)    1/42 (2%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   317          718          570          587       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.366N     P=0.409N     P=0.440N     P=0.426N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.576N     P=0.682N     P=0.555N     P=0.659    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.429N     P=0.448N     P=0.443N     P=0.514N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.433N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.472N     P=0.472N     P=0.524N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  28
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                                       |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   0/70 (0%)    1/70 (1%)    4/100 (4%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         4.3%         7.5%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    1/23 (4%)    2/42 (5%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      388       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.009 **     (e)        P=0.380      P=0.050    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.005 **     (e)        P=0.380      P=0.026 *  |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.005 **     (e)        P=0.380      P=0.030 *  |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.004 **                                        |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.327      P=0.027 *  |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/144 (0%)   0/70 (0%)    1/70 (1%)    4/100 (4%) |  0/132 (0%)   0/70 (0%)    0/70 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         4.3%         7.5%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/25 (0%)    1/23 (4%)    2/42 (5%)  |  0/59 (0%)    0/31 (0%)    0/34 (0%)    0/54 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      388       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.009 **     (e)        P=0.380      P=0.050    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.005 **     (e)        P=0.380      P=0.026 *  |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.005 **     (e)        P=0.380      P=0.030 *  |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.004 **                                        |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.327      P=0.027 *  |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  29
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            |112/144 (78%) 56/70 (80%)  54/70 (77%)  83/100 (83%)| 80/132 (61%) 39/70 (56%)  40/70 (57%)  61/100 (61%)|
|ADJUSTED (b)           | 100.0%       100.0%        98.2%       100.0%      |  90.7%        80.6%        86.4%        80.2%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  3/9 (33%)    7/9 (78%)    7/10 (70%)   7/10 (70%) |  0/10 (0%)    3/10 (30%)   3/10 (30%)   2/9 (22%)  |
|TERMINAL (d)           | 42/42 (100%) 25/25 (100%) 22/23 (96%)  42/42 (100%)| 51/59 (86%)  22/31 (71%)  28/34 (82%)  39/54 (72%) |
|FIRST INCIDENCE (DAYS) |   414          459 (I)      404          459 (I)   |   376          459 (I)      460 (I)      459 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.041N*    P=0.118N     P=0.176N     P=0.035N*  |  P=0.100N     P=0.277N     P=0.182N     P=0.101N   |
|INCIDENTAL TUMOR       |  P=0.226      P=0.199      P=0.301      P=0.166    |  P=0.417N     P=0.506N     P=0.509N     P=0.425N   |
|LOGISTIC REGRESSION    |  P=0.154      P=0.141      P=0.210      P=0.163    |  P=0.379N     P=0.380N     P=0.474N     P=0.344N   |
|COCHRAN-ARMITAGE       |  P=0.223                                           |  P=0.449                                           |
|FISHER EXACT           |               P=0.428      P=0.523N     P=0.201    |               P=0.300N     P=0.371N     P=0.530    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 83/144 (58%) 31/70 (44%)  29/70 (41%)  63/100 (63%)| 46/132 (35%) 21/70 (30%)  25/70 (36%)  32/100 (32%)|
|ADJUSTED (b)           |  85.3%        66.0%        64.8%        81.4%      |  53.5%        46.9%        54.7%        43.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  3/9 (33%)    0/9 (0%)     3/10 (30%)   1/10 (10%) |  0/10 (0%)    1/10 (10%)   1/10 (10%)   2/9 (22%)  |
|TERMINAL (d)           | 29/42 (69%)  10/25 (40%)   9/23 (39%)  28/42 (67%) | 22/59 (37%)   9/31 (29%)  14/34 (41%)  14/54 (26%) |
|FIRST INCIDENCE (DAYS) |   180          422          459 (I)      282       |   320          451          460 (I)      338       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.250N     P=0.015N*    P=0.012N*    P=0.155N   |  P=0.184N     P=0.294N     P=0.501N     P=0.156N   |
|INCIDENTAL TUMOR       |  P=0.059      P=0.132N     P=0.041N*    P=0.098    |  P=0.468      P=0.557N     P=0.241      P=0.512N   |
|LOGISTIC REGRESSION    |  P=0.213      P=0.027N*    P=0.019N*    P=0.348    |  P=0.432N     P=0.334N     P=0.456      P=0.312N   |
|COCHRAN-ARMITAGE       |  P=0.206                                           |  P=0.447N                                          |
|FISHER EXACT           |               P=0.045N*    P=0.019N*    P=0.240    |               P=0.296N     P=0.511      P=0.377N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05131 TEST: 01                                                 PAGE  30
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            |118/144 (82%) 58/70 (83%)  56/70 (80%)  88/100 (88%)| 95/132 (72%) 45/70 (64%)  51/70 (73%)  74/100 (74%)|
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  94.9%        86.1%        96.2%        91.3%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/1 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  4/9 (44%)    7/9 (78%)    8/10 (80%)   8/10 (80%) |  0/10 (0%)    4/10 (40%)   3/10 (30%)   3/9 (33%)  |
|TERMINAL (d)           | 42/42 (100%) 25/25 (100%) 23/23 (100%) 42/42 (100%)| 54/59 (92%)  24/31 (77%)  32/34 (94%)  47/54 (87%) |
|FIRST INCIDENCE (DAYS) |   180          422          404          282       |   320          451          460 (I)      338       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.052N     P=0.096N     P=0.131N     P=0.046N*  |  P=0.160N     P=0.188N     P=0.366N     P=0.118N   |
|INCIDENTAL TUMOR       |  P=0.021 *    P=0.055      P=0.299      P=0.011 *  |  P=0.177      P=0.574N     P=0.043 *    P=0.374    |
|LOGISTIC REGRESSION    |  P=0.048 *    P=0.254      P=0.332      P=0.064    |  P=0.363      P=0.235N     P=0.278      P=0.554N   |
|COCHRAN-ARMITAGE       |  P=0.155                                           |  P=0.244                                           |
|FISHER EXACT           |               P=0.516      P=0.433N     P=0.134    |               P=0.167N     P=0.515      P=0.424    |
|=================================================================================================================================|
 
 (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):   190  459
          Female interim sacrifices(days): 184  459
 (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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