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TDMS Study 05085-02 Pathology Tables


NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                      MANGANESE SULFATE                                  DATE: 09/11/94       
EXPERIMENT: 05085 TEST: 02                                                                                     TIME: 05:11:58       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 61143B       
PATHOLOGIST: R. PERSING                                                                                        CAS: 7785-87-7       
------------------------------------------------------------------------------------------------------------------------------------
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Battelle Columbus                                      MANGANESE SULFATE                                  DATE: 09/11/94      
EXPERIMENT: 05085 TEST: 02                                                                                     TIME: 05:11:58      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 61143B      
PATHOLOGIST: R. PERSING                                                                                        CAS: 7785-87-7      
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                    ----------------
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                      MANGANESE SULFATE                                  DATE: 09/11/94       
EXPERIMENT: 05085 TEST: 02                                                                                     TIME: 05:11:58       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 61143B       
PATHOLOGIST: R. PERSING                                                                                        CAS: 7785-87-7       
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                       IN THE ANALYSIS OF THE STUDY OF MANGANESE SULFATE
              ====================================================================================================
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
                             Adrenal Gland: Non-medullary, Non-cortical
                                                           Adenoma
                             Harderian Gland               Carcinoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Thyroid Gland: Follicular Cell
                                                           Adenoma
                             All Organs                    Benign Tumors
                                                           Malignant and Benign Tumors
              ====================================================================================================
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
                             Thyroid Gland: Follicular Cell
                                                           Adenoma
              ====================================================================================================
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   1
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/69 (0%)    3/60 (5%)    1/61 (2%)    1/68 (1%)  |  0/70 (0%)    0/61 (0%)    0/60 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         6.8%         2.2%         2.2%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/45 (0%)    3/44 (7%)    1/46 (2%)    1/45 (2%)  |  0/42 (0%)    0/46 (0%)    0/36 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      729 (T)      729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.578N     P=0.117      P=0.504      P=0.500    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.578N     P=0.117      P=0.504      P=0.500    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.578N     P=0.117      P=0.504      P=0.500    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.562N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.098      P=0.469      P=0.496    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Gland: Non-medullary, Non-cortical                                                                                       |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/70 (14%)   5/60 (8%)    7/61 (11%)  14/68 (21%) |  0/70 (0%)    2/61 (3%)    3/62 (5%)    0/70 (0%)  |
|ADJUSTED (b)           |  21.7%        11.4%        15.2%        31.1%      |   0.0%         4.3%         7.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 10/46 (22%)   5/44 (11%)   7/46 (15%)  14/45 (31%) |  0/42 (0%)    2/46 (4%)    3/38 (8%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   ---          729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.042 *    P=0.151N     P=0.297N     P=0.220    |  P=0.395N     P=0.259      P=0.104        (e)      |
|INCIDENTAL TUMOR       |  P=0.042 *    P=0.151N     P=0.297N     P=0.220    |  P=0.395N     P=0.259      P=0.104        (e)      |
|LOGISTIC REGRESSION    |  P=0.042 *    P=0.151N     P=0.297N     P=0.220    |  P=0.395N     P=0.259      P=0.104        (e)      |
|COCHRAN-ARMITAGE       |  P=0.063                                           |  P=0.364N                                          |
|FISHER EXACT           |               P=0.218N     P=0.416N     P=0.226    |               P=0.215      P=0.101        (e)      |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   2
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    1/62 (2%)    2/70 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         2.3%         4.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    1/42 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          693          696       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.082        (e)        P=0.496      P=0.240    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.105        (e)        P=0.638      P=0.295    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.086        (e)        P=0.491      P=0.243    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.096                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.470      P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    1/60 (2%)    0/61 (0%)    0/69 (0%)  |  0/70 (0%)    3/61 (5%)    0/62 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         2.3%         0.0%         0.0%      |   0.0%         6.5%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    1/44 (2%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    3/46 (7%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.573N     P=0.491        (e)          (e)      |  P=0.264N     P=0.138        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.573N     P=0.491        (e)          (e)      |  P=0.264N     P=0.138        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.573N     P=0.491        (e)          (e)      |  P=0.264N     P=0.138        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.566N                                          |  P=0.247N                                          |
|FISHER EXACT           |               P=0.462        (e)          (e)      |               P=0.098        (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   3
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/70 (7%)    2/60 (3%)    2/61 (3%)    1/70 (1%)  |  2/70 (3%)    3/61 (5%)    2/62 (3%)    0/70 (0%)  |
|ADJUSTED (b)           |  10.2%         4.3%         4.2%         2.2%      |   4.8%         6.5%         5.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  4/46 (9%)    1/44 (2%)    1/46 (2%)    1/46 (2%)  |  2/42 (5%)    3/46 (7%)    2/38 (5%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   452 (I)      617          592          729 (T)   |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.125N     P=0.234N     P=0.227N     P=0.106N   |  P=0.125N     P=0.541      P=0.658      P=0.238N   |
|INCIDENTAL TUMOR       |  P=0.078N     P=0.115N     P=0.110N     P=0.106N   |  P=0.125N     P=0.541      P=0.658      P=0.238N   |
|LOGISTIC REGRESSION    |  P=0.087N     P=0.140N     P=0.170N     P=0.107N   |  P=0.125N     P=0.541      P=0.658      P=0.237N   |
|COCHRAN-ARMITAGE       |  P=0.115N                                          |  P=0.110N                                          |
|FISHER EXACT           |               P=0.289N     P=0.281N     P=0.104N   |               P=0.435      P=0.643      P=0.248N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/60 (0%)    0/61 (0%)    4/70 (6%)  |  1/70 (1%)    0/61 (0%)    0/62 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   2.2%         0.0%         0.0%         8.4%      |   2.4%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/46 (2%)    0/44 (0%)    0/46 (0%)    3/46 (7%)  |  1/42 (2%)    0/46 (0%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          634       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.016 *    P=0.509N     P=0.500N     P=0.182    |  P=0.480N     P=0.482N     P=0.520N     P=0.500N   |
|INCIDENTAL TUMOR       |  P=0.022 *    P=0.509N     P=0.500N     P=0.306    |  P=0.480N     P=0.482N     P=0.520N     P=0.500N   |
|LOGISTIC REGRESSION    |  P=0.015 *    P=0.509N     P=0.500N     P=0.175    |  P=0.480N     P=0.482N     P=0.520N     P=0.500N   |
|COCHRAN-ARMITAGE       |  P=0.020 *                                         |  P=0.465N                                          |
|FISHER EXACT           |               P=0.538N     P=0.534N     P=0.183    |               P=0.534N     P=0.530N     P=0.500N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   4
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/70 (9%)    2/60 (3%)    2/61 (3%)    5/70 (7%)  |  3/70 (4%)    3/61 (5%)    2/62 (3%)    0/70 (0%)  |
|ADJUSTED (b)           |  12.4%         4.3%         4.2%        10.6%      |   7.1%         6.5%         5.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  5/46 (11%)   1/44 (2%)    1/46 (2%)    4/46 (9%)  |  3/42 (7%)    3/46 (7%)    2/38 (5%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   452 (I)      617          592          634       |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.466      P=0.150N     P=0.144N     P=0.500N   |  P=0.080N     P=0.620N     P=0.546N     P=0.121N   |
|INCIDENTAL TUMOR       |  P=0.570      P=0.067N     P=0.063N     P=0.371N   |  P=0.080N     P=0.620N     P=0.546N     P=0.121N   |
|LOGISTIC REGRESSION    |  P=0.546      P=0.085N     P=0.104N     P=0.509N   |  P=0.080N     P=0.620N     P=0.546N     P=0.121N   |
|COCHRAN-ARMITAGE       |  P=0.501                                           |  P=0.070N                                          |
|FISHER EXACT           |               P=0.193N     P=0.186N     P=0.500N   |               P=0.592      P=0.558N     P=0.122N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/60 (3%)    0/61 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   0.0%         4.4%         0.0%         0.0%      |   0.0%         0.0%         0.0%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    1/44 (2%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    1/42 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          679          ---          ---       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.372N     P=0.230        (e)          (e)      |  P=0.211        (e)          (e)        P=0.500    |
|INCIDENTAL TUMOR       |  P=0.420N     P=0.266        (e)          (e)      |  P=0.211        (e)          (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.369N     P=0.228        (e)          (e)      |  P=0.211        (e)          (e)        P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.358N                                          |  P=0.227                                           |
|FISHER EXACT           |               P=0.211        (e)          (e)      |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   5
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/60 (3%)    0/61 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         4.4%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    1/44 (2%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          679          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.372N     P=0.230        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.420N     P=0.266        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.369N     P=0.228        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.358N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.211        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    2/60 (3%)    0/69 (0%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         4.3%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    2/46 (4%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.693N       (e)        P=0.239        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.693N       (e)        P=0.239        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.693N       (e)        P=0.239        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.682N                                          |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.211        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   6
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 31/70 (44%)  29/60 (48%)  19/61 (31%)  21/69 (30%) | 12/70 (17%)  14/61 (23%)   8/62 (13%)  12/70 (17%) |
|ADJUSTED (b)           |  64.3%        64.4%        40.4%        43.5%      |  27.8%        29.7%        18.2%        27.9%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/10 (10%) |  0/9 (0%)     0/10 (0%)    2/9 (22%)    0/9 (0%)   |
|TERMINAL (d)           | 29/46 (63%)  28/44 (64%)  18/46 (39%)  19/46 (41%) | 11/42 (26%)  13/46 (28%)   5/38 (13%)  11/42 (26%) |
|FIRST INCIDENCE (DAYS) |   276 (I)      708          702          452 (I)   |   607          701          452 (I)      726       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.023N*    P=0.570      P=0.022N*    P=0.044N*  |  P=0.528N     P=0.516      P=0.299N     P=0.590N   |
|INCIDENTAL TUMOR       |  P=0.028N*    P=0.566N     P=0.025N*    P=0.049N*  |  P=0.503N     P=0.429      P=0.252N     P=0.585    |
|LOGISTIC REGRESSION    |  P=0.032N*    P=0.483N     P=0.018N*    P=0.048N*  |  P=0.486N     P=0.505      P=0.262N     P=0.567N   |
|COCHRAN-ARMITAGE       |  P=0.026N*                                         |  P=0.415N                                          |
|FISHER EXACT           |               P=0.388      P=0.086N     P=0.065N   |               P=0.270      P=0.333N     P=0.589N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  9/70 (13%)  12/60 (20%)   8/61 (13%)   6/69 (9%)  |  3/70 (4%)    1/61 (2%)    1/62 (2%)    2/70 (3%)  |
|ADJUSTED (b)           |  18.7%        26.1%        16.3%        13.0%      |   6.8%         2.2%         2.4%         4.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  7/46 (15%)  10/44 (23%)   6/46 (13%)   6/46 (13%) |  2/42 (5%)    1/46 (2%)    0/38 (0%)    2/42 (5%)  |
|FIRST INCIDENCE (DAYS) |   466          701          417          729 (T)   |   607          729 (T)      702          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.131N     P=0.280      P=0.501N     P=0.294N   |  P=0.612N     P=0.278N     P=0.332N     P=0.498N   |
|INCIDENTAL TUMOR       |  P=0.135N     P=0.230      P=0.545N     P=0.310N   |  P=0.602N     P=0.468N     P=0.232N     P=0.561N   |
|LOGISTIC REGRESSION    |  P=0.135N     P=0.283      P=0.541N     P=0.302N   |  P=0.599N     P=0.295N     P=0.321N     P=0.490N   |
|COCHRAN-ARMITAGE       |  P=0.115N                                          |  P=0.573N                                          |
|FISHER EXACT           |               P=0.194      P=0.584      P=0.303N   |               P=0.363N     P=0.357N     P=0.500N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   7
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 35/70 (50%)  31/60 (52%)  24/61 (39%)  23/69 (33%) | 13/70 (19%)  15/61 (25%)   9/62 (15%)  13/70 (19%) |
|ADJUSTED (b)           |  71.2%        67.4%        48.8%        47.7%      |  30.1%        31.9%        20.2%        30.2%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/10 (10%) |  0/9 (0%)     0/10 (0%)    2/9 (22%)    0/9 (0%)   |
|TERMINAL (d)           | 32/46 (70%)  29/44 (66%)  21/46 (46%)  21/46 (46%) | 12/42 (29%)  14/46 (30%)   5/38 (13%)  12/42 (29%) |
|FIRST INCIDENCE (DAYS) |   276 (I)      701          417          452 (I)   |   607          701          452 (I)      726       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.014N*    P=0.441N     P=0.042N*    P=0.019N*  |  P=0.531N     P=0.523      P=0.313N     P=0.588N   |
|INCIDENTAL TUMOR       |  P=0.014N*    P=0.478N     P=0.041N*    P=0.021N*  |  P=0.497N     P=0.439      P=0.238N     P=0.583    |
|LOGISTIC REGRESSION    |  P=0.017N*    P=0.328N     P=0.035N*    P=0.021N*  |  P=0.487N     P=0.513      P=0.271N     P=0.564N   |
|COCHRAN-ARMITAGE       |  P=0.014N*                                         |  P=0.412N                                          |
|FISHER EXACT           |               P=0.495      P=0.148N     P=0.034N*  |               P=0.266      P=0.350N     P=0.586N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 35/70 (50%)  31/60 (52%)  24/61 (39%)  23/69 (33%) | 13/70 (19%)  15/61 (25%)   9/62 (15%)  13/70 (19%) |
|ADJUSTED (b)           |  71.2%        67.4%        48.8%        47.7%      |  30.1%        31.9%        20.2%        30.2%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/10 (10%) |  0/9 (0%)     0/10 (0%)    2/9 (22%)    0/9 (0%)   |
|TERMINAL (d)           | 32/46 (70%)  29/44 (66%)  21/46 (46%)  21/46 (46%) | 12/42 (29%)  14/46 (30%)   5/38 (13%)  12/42 (29%) |
|FIRST INCIDENCE (DAYS) |   276 (I)      701          417          452 (I)   |   607          701          452 (I)      726       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.014N*    P=0.441N     P=0.042N*    P=0.019N*  |  P=0.531N     P=0.523      P=0.313N     P=0.588N   |
|INCIDENTAL TUMOR       |  P=0.014N*    P=0.478N     P=0.041N*    P=0.021N*  |  P=0.497N     P=0.439      P=0.238N     P=0.583    |
|LOGISTIC REGRESSION    |  P=0.017N*    P=0.328N     P=0.035N*    P=0.021N*  |  P=0.487N     P=0.513      P=0.271N     P=0.564N   |
|COCHRAN-ARMITAGE       |  P=0.014N*                                         |  P=0.412N                                          |
|FISHER EXACT           |               P=0.495      P=0.148N     P=0.034N*  |               P=0.266      P=0.350N     P=0.586N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   8
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/70 (11%)  10/60 (17%)   5/61 (8%)    9/69 (13%) |  2/70 (3%)    4/61 (7%)    3/62 (5%)    4/70 (6%)  |
|ADJUSTED (b)           |  16.4%        21.6%        10.9%        20.0%      |   4.8%         8.5%         7.9%         9.2%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  7/46 (15%)   8/44 (18%)   5/46 (11%)   9/45 (20%) |  2/42 (5%)    3/46 (7%)    3/38 (8%)    3/42 (7%)  |
|FIRST INCIDENCE (DAYS) |   276 (I)      647          729 (T)      729 (T)   |   729 (T)      720          729 (T)      689       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.536      P=0.286      P=0.360N     P=0.476    |  P=0.364      P=0.381      P=0.454      P=0.340    |
|INCIDENTAL TUMOR       |  P=0.509      P=0.313      P=0.360N     P=0.476    |  P=0.395      P=0.396      P=0.454      P=0.377    |
|LOGISTIC REGRESSION    |  P=0.505      P=0.352      P=0.308N     P=0.469    |  P=0.375      P=0.380      P=0.454      P=0.347    |
|COCHRAN-ARMITAGE       |  P=0.550N                                          |  P=0.420                                           |
|FISHER EXACT           |               P=0.271      P=0.375N     P=0.487    |               P=0.277      P=0.442      P=0.340    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/70 (7%)    4/60 (7%)    4/61 (7%)    4/69 (6%)  |  4/70 (6%)    0/61 (0%)    3/62 (5%)    0/70 (0%)  |
|ADJUSTED (b)           |  10.9%         9.1%         8.7%         8.9%      |   9.2%         0.0%         7.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  5/46 (11%)   4/44 (9%)    4/46 (9%)    4/45 (9%)  |  3/42 (7%)    0/46 (0%)    3/38 (8%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   620          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.497N     P=0.528N     P=0.500N     P=0.514N   |  P=0.132N     P=0.054N     P=0.550N     P=0.064N   |
|INCIDENTAL TUMOR       |  P=0.497N     P=0.528N     P=0.500N     P=0.514N   |  P=0.133N     P=0.106N     P=0.516N     P=0.086N   |
|LOGISTIC REGRESSION    |  P=0.497N     P=0.528N     P=0.500N     P=0.514N   |  P=0.124N     P=0.058N     P=0.518N     P=0.060N   |
|COCHRAN-ARMITAGE       |  P=0.458N                                          |  P=0.117N                                          |
|FISHER EXACT           |               P=0.597N     P=0.587N     P=0.509N   |               P=0.078N     P=0.568N     P=0.060N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE   9
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/70 (19%)  13/60 (22%)   9/61 (15%)  12/69 (17%) |  6/70 (9%)    4/61 (7%)    6/62 (10%)   4/70 (6%)  |
|ADJUSTED (b)           |  27.1%        28.1%        19.6%        26.7%      |  13.8%         8.5%        15.8%         9.2%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 12/46 (26%)  11/44 (25%)   9/46 (20%)  12/45 (27%) |  5/42 (12%)   3/46 (7%)    6/38 (16%)   3/42 (7%)  |
|FIRST INCIDENCE (DAYS) |   276 (I)      647          729 (T)      729 (T)   |   620          720          729 (T)      689       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.457N     P=0.468      P=0.297N     P=0.529N   |  P=0.421N     P=0.318N     P=0.552      P=0.368N   |
|INCIDENTAL TUMOR       |  P=0.481N     P=0.496      P=0.297N     P=0.529N   |  P=0.400N     P=0.430N     P=0.579      P=0.381N   |
|LOGISTIC REGRESSION    |  P=0.498N     P=0.544      P=0.260N     P=0.543N   |  P=0.403N     P=0.327N     P=0.597      P=0.355N   |
|COCHRAN-ARMITAGE       |  P=0.404N                                          |  P=0.358N                                          |
|FISHER EXACT           |               P=0.412      P=0.365N     P=0.516N   |               P=0.462N     P=0.531      P=0.372N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/70 (0%)    2/61 (3%)    0/62 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |                                                    |   0.0%         4.3%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  0/42 (0%)    2/46 (4%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.378N     P=0.259        (e)          (e)      |
|INCIDENTAL TUMOR       |                                                    |  P=0.378N     P=0.259        (e)          (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.378N     P=0.259        (e)          (e)      |
|COCHRAN-ARMITAGE       |                                                    |  P=0.359N                                          |
|FISHER EXACT           |                                                    |               P=0.215        (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  10
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/70 (3%)    0/61 (0%)    1/62 (2%)    2/70 (3%)  |
|ADJUSTED (b)           |                                                    |   4.8%         0.0%         2.6%         4.8%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  2/42 (5%)    0/46 (0%)    1/38 (3%)    2/42 (5%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   729 (T)      ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.392      P=0.219N     P=0.535N     P=0.695    |
|INCIDENTAL TUMOR       |                                                    |  P=0.392      P=0.219N     P=0.535N     P=0.695    |
|LOGISTIC REGRESSION    |                                                    |  P=0.392      P=0.219N     P=0.535N     P=0.695    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.428                                           |
|FISHER EXACT           |                                                    |               P=0.284N     P=0.546N     P=0.690N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/66 (0%)    0/55 (0%)    0/59 (0%)    0/65 (0%)  |  2/67 (3%)    3/57 (5%)    6/62 (10%)   5/68 (7%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   5.1%         6.7%        15.8%        12.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/39 (0%)    0/45 (0%)    0/43 (0%)  |  2/39 (5%)    2/42 (5%)    6/38 (16%)   5/40 (13%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   729 (T)      712          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.202      P=0.537      P=0.125      P=0.226    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.213      P=0.553      P=0.125      P=0.226    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.206      P=0.533      P=0.125      P=0.226    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.254                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.423      P=0.113      P=0.226    |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  11
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Intermedia                                                                                                 |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/66 (0%)    0/55 (0%)    0/59 (0%)    0/65 (0%)  |  0/67 (0%)    0/57 (0%)    2/62 (3%)    1/68 (1%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         5.3%         2.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/39 (0%)    0/45 (0%)    0/43 (0%)  |  0/39 (0%)    0/42 (0%)    2/38 (5%)    0/40 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          729 (T)      473       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.353        (e)        P=0.233      P=0.508    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.446        (e)        P=0.233      P=0.581    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.372        (e)        P=0.233      P=0.492    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.375                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.229      P=0.504    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  2/70 (3%)    0/61 (0%)    0/62 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.4%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   607          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.247N     P=0.223N     P=0.250N     P=0.237N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.210N     P=0.443N     P=0.130N     P=0.249N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.239N     P=0.249N     P=0.253N     P=0.235N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.237N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.284N     P=0.279N     P=0.248N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  12
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  1/70 (1%)    0/61 (0%)    3/62 (5%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   2.2%         0.0%         5.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   696          ---          409          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.449N     P=0.483N     P=0.304      P=0.500N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.272N     P=0.443N     P=0.397      P=0.398N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.424N     P=0.496N     P=0.231      P=0.496N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.431N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.534N     P=0.265      P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  3/70 (4%)    0/61 (0%)    3/62 (5%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   6.5%         0.0%         5.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   607          ---          409          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.198N     P=0.111N     P=0.648      P=0.123N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.085N     P=0.157N     P=0.487N     P=0.085N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.172N     P=0.124N     P=0.614N     P=0.118N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.183N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.150N     P=0.601      P=0.122N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  13
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  3/70 (4%)    0/61 (0%)    3/62 (5%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   6.5%         0.0%         5.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   607          ---          409          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.198N     P=0.111N     P=0.648      P=0.123N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.085N     P=0.157N     P=0.487N     P=0.085N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.172N     P=0.124N     P=0.614N     P=0.118N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.183N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.150N     P=0.601      P=0.122N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/60 (3%)    0/60 (0%)    0/69 (0%)  |  1/70 (1%)    0/61 (0%)    0/62 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         4.5%         0.0%         0.0%      |   2.4%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    2/44 (5%)    0/46 (0%)    0/46 (0%)  |  1/42 (2%)    0/46 (0%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.366N     P=0.229        (e)          (e)      |  P=0.480N     P=0.482N     P=0.520N     P=0.500N   |
|INCIDENTAL TUMOR       |  P=0.366N     P=0.229        (e)          (e)      |  P=0.480N     P=0.482N     P=0.520N     P=0.500N   |
|LOGISTIC REGRESSION    |  P=0.366N     P=0.229        (e)          (e)      |  P=0.480N     P=0.482N     P=0.520N     P=0.500N   |
|COCHRAN-ARMITAGE       |  P=0.361N                                          |  P=0.465N                                          |
|FISHER EXACT           |               P=0.211        (e)          (e)      |               P=0.534N     P=0.530N     P=0.500N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  14
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    1/60 (2%)    2/60 (3%)    0/69 (0%)  |  0/70 (0%)    2/61 (3%)    0/62 (0%)    2/70 (3%)  |
|ADJUSTED (b)           |   0.0%         2.3%         4.3%         0.0%      |   0.0%         4.3%         0.0%         4.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    1/44 (2%)    2/46 (4%)    0/46 (0%)  |  0/42 (0%)    2/46 (4%)    0/38 (0%)    1/42 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      729 (T)      ---       |   ---          729 (T)      ---          631       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.510N     P=0.491      P=0.239        (e)      |  P=0.284      P=0.259        (e)        P=0.247    |
|INCIDENTAL TUMOR       |  P=0.510N     P=0.491      P=0.239        (e)      |  P=0.264      P=0.259        (e)        P=0.166    |
|LOGISTIC REGRESSION    |  P=0.510N     P=0.491      P=0.239        (e)      |  P=0.290      P=0.259        (e)        P=0.242    |
|COCHRAN-ARMITAGE       |  P=0.500N                                          |  P=0.309                                           |
|FISHER EXACT           |               P=0.462      P=0.211        (e)      |               P=0.215        (e)        P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    4/69 (6%)  |  2/69 (3%)    1/61 (2%)    0/61 (0%)    5/70 (7%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         8.3%      |   4.8%         2.2%         0.0%        11.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/10 (10%) |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    0/46 (0%)    3/46 (7%)  |  2/42 (5%)    1/46 (2%)    0/37 (0%)    5/42 (12%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          453 (I)   |   729 (T)      729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002 **     (e)          (e)        P=0.065    |  P=0.037 *    P=0.468N     P=0.267N     P=0.216    |
|INCIDENTAL TUMOR       |  P=0.002 **     (e)          (e)        P=0.065    |  P=0.037 *    P=0.468N     P=0.267N     P=0.216    |
|LOGISTIC REGRESSION    |  P=0.003 **     (e)          (e)        P=0.062    |  P=0.037 *    P=0.468N     P=0.267N     P=0.216    |
|COCHRAN-ARMITAGE       |  P=0.003 **                                        |  P=0.052                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.058    |               P=0.546N     P=0.280N     P=0.226    |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  15
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/70 (0%)    2/61 (3%)    0/62 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |                                                    |   0.0%         4.1%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  0/42 (0%)    1/46 (2%)    0/38 (0%)    0/42 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          679          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.376N     P=0.262        (e)          (e)      |
|INCIDENTAL TUMOR       |                                                    |  P=0.337N     P=0.282        (e)          (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.369N     P=0.245        (e)          (e)      |
|COCHRAN-ARMITAGE       |                                                    |  P=0.359N                                          |
|FISHER EXACT           |                                                    |               P=0.215        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/70 (1%)    1/61 (2%)    0/62 (0%)    2/70 (3%)  |
|ADJUSTED (b)           |                                                    |   2.4%         2.2%         0.0%         4.8%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  1/42 (2%)    1/46 (2%)    0/38 (0%)    2/42 (5%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   729 (T)      729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.323      P=0.741N     P=0.520N     P=0.500    |
|INCIDENTAL TUMOR       |                                                    |  P=0.323      P=0.741N     P=0.520N     P=0.500    |
|LOGISTIC REGRESSION    |                                                    |  P=0.323      P=0.741N     P=0.520N     P=0.500    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.355                                           |
|FISHER EXACT           |                                                    |               P=0.716      P=0.530N     P=0.500    |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  16
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/70 (1%)    2/61 (3%)    0/62 (0%)    2/70 (3%)  |
|ADJUSTED (b)           |                                                    |   2.4%         4.3%         0.0%         4.8%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  1/42 (2%)    2/46 (4%)    0/38 (0%)    2/42 (5%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   729 (T)      729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.453      P=0.532      P=0.520N     P=0.500    |
|INCIDENTAL TUMOR       |                                                    |  P=0.453      P=0.532      P=0.520N     P=0.500    |
|LOGISTIC REGRESSION    |                                                    |  P=0.453      P=0.532      P=0.520N     P=0.500    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.488                                           |
|FISHER EXACT           |                                                    |               P=0.448      P=0.530N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    5/60 (8%)    3/61 (5%)    1/70 (1%)  |  2/70 (3%)    4/61 (7%)    0/62 (0%)    3/70 (4%)  |
|ADJUSTED (b)           |   2.2%        11.0%         6.5%         2.2%      |   4.8%         8.7%         0.0%         6.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/46 (2%)    4/44 (9%)    3/46 (7%)    1/46 (2%)  |  2/42 (5%)    4/46 (9%)    0/38 (0%)    2/42 (5%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      647          729 (T)      729 (T)   |   729 (T)      729 (T)      ---          631       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.263N     P=0.097      P=0.306      P=0.761    |  P=0.541      P=0.380      P=0.261N     P=0.506    |
|INCIDENTAL TUMOR       |  P=0.281N     P=0.108      P=0.306      P=0.761    |  P=0.531      P=0.380      P=0.261N     P=0.439    |
|LOGISTIC REGRESSION    |  P=0.270N     P=0.096      P=0.306      P=0.761    |  P=0.552      P=0.380      P=0.261N     P=0.511    |
|COCHRAN-ARMITAGE       |  P=0.245N                                          |  P=0.582                                           |
|FISHER EXACT           |               P=0.073      P=0.260      P=0.752N   |               P=0.277      P=0.279N     P=0.500    |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  17
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    5/60 (8%)    3/61 (5%)    1/70 (1%)  |  3/70 (4%)    4/61 (7%)    0/62 (0%)    3/70 (4%)  |
|ADJUSTED (b)           |   2.2%        11.0%         6.5%         2.2%      |   7.1%         8.7%         0.0%         6.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/46 (2%)    4/44 (9%)    3/46 (7%)    1/46 (2%)  |  3/42 (7%)    4/46 (9%)    0/38 (0%)    2/42 (5%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      647          729 (T)      729 (T)   |   729 (T)      729 (T)      ---          631       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.263N     P=0.097      P=0.306      P=0.761    |  P=0.564N     P=0.550      P=0.139N     P=0.657N   |
|INCIDENTAL TUMOR       |  P=0.281N     P=0.108      P=0.306      P=0.761    |  P=0.575N     P=0.550      P=0.139N     P=0.610    |
|LOGISTIC REGRESSION    |  P=0.270N     P=0.096      P=0.306      P=0.761    |  P=0.553N     P=0.550      P=0.139N     P=0.652N   |
|COCHRAN-ARMITAGE       |  P=0.245N                                          |  P=0.517N                                          |
|FISHER EXACT           |               P=0.073      P=0.260      P=0.752N   |               P=0.423      P=0.146N     P=0.660N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/70 (7%)    4/60 (7%)    5/61 (8%)    2/70 (3%)  | 15/70 (21%)  17/61 (28%)  21/62 (34%)  13/70 (19%) |
|ADJUSTED (b)           |  10.6%         9.1%        10.9%         4.2%      |  32.8%        37.0%        47.4%        28.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  4/46 (9%)    4/44 (9%)    5/46 (11%)   1/46 (2%)  | 12/42 (29%)  17/46 (37%)  15/38 (39%)  10/42 (24%) |
|FIRST INCIDENCE (DAYS) |   709          729 (T)      729 (T)      645       |   323          729 (T)      554          676       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.183N     P=0.530N     P=0.628      P=0.225N   |  P=0.318N     P=0.533      P=0.105      P=0.412N   |
|INCIDENTAL TUMOR       |  P=0.207N     P=0.505N     P=0.604      P=0.261N   |  P=0.278N     P=0.367      P=0.164      P=0.393N   |
|LOGISTIC REGRESSION    |  P=0.191N     P=0.526N     P=0.624      P=0.225N   |  P=0.268N     P=0.485      P=0.123      P=0.385N   |
|COCHRAN-ARMITAGE       |  P=0.166N                                          |  P=0.211N                                          |
|FISHER EXACT           |               P=0.597N     P=0.538      P=0.221N   |               P=0.257      P=0.080      P=0.416N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  18
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/70 (7%)    4/60 (7%)    5/61 (8%)    2/70 (3%)  | 15/70 (21%)  17/61 (28%)  21/62 (34%)  13/70 (19%) |
|ADJUSTED (b)           |  10.6%         9.1%        10.9%         4.2%      |  32.8%        37.0%        47.4%        28.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  4/46 (9%)    4/44 (9%)    5/46 (11%)   1/46 (2%)  | 12/42 (29%)  17/46 (37%)  15/38 (39%)  10/42 (24%) |
|FIRST INCIDENCE (DAYS) |   709          729 (T)      729 (T)      645       |   323          729 (T)      554          676       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.183N     P=0.530N     P=0.628      P=0.225N   |  P=0.318N     P=0.533      P=0.105      P=0.412N   |
|INCIDENTAL TUMOR       |  P=0.207N     P=0.505N     P=0.604      P=0.261N   |  P=0.278N     P=0.367      P=0.164      P=0.393N   |
|LOGISTIC REGRESSION    |  P=0.191N     P=0.526N     P=0.624      P=0.225N   |  P=0.268N     P=0.485      P=0.123      P=0.385N   |
|COCHRAN-ARMITAGE       |  P=0.166N                                          |  P=0.211N                                          |
|FISHER EXACT           |               P=0.597N     P=0.538      P=0.221N   |               P=0.257      P=0.080      P=0.416N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    1/62 (2%)    2/70 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         2.3%         4.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    1/42 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          693          696       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.082        (e)        P=0.496      P=0.240    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.105        (e)        P=0.638      P=0.295    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.086        (e)        P=0.491      P=0.243    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.096                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.470      P=0.248    |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  19
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    1/62 (2%)    2/70 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         2.3%         4.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/46 (0%)    0/44 (0%)    0/46 (0%)    0/46 (0%)  |  0/42 (0%)    0/46 (0%)    0/38 (0%)    1/42 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          693          696       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.082        (e)        P=0.496      P=0.240    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.105        (e)        P=0.638      P=0.295    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.086        (e)        P=0.491      P=0.243    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.096                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.470      P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 41/70 (59%)  40/60 (67%)  31/61 (51%)  34/70 (49%) | 21/70 (30%)  24/61 (39%)  18/62 (29%)  25/70 (36%) |
|ADJUSTED (b)           |  81.7%        81.5%        63.3%        69.2%      |  48.7%        49.0%        43.0%        55.4%      |
|INTERIM SACRIFICE 1 (c)|  2/10 (20%)   1/1 (100%)   0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/9 (0%)     2/10 (20%) |  0/9 (0%)     0/10 (0%)    2/9 (22%)    0/9 (0%)   |
|TERMINAL (d)           | 37/46 (80%)  35/44 (80%)  28/46 (61%)  31/46 (67%) | 20/42 (48%)  21/46 (46%)  15/38 (39%)  22/42 (52%) |
|FIRST INCIDENCE (DAYS) |   276 (I)      276 (I)      592          452 (I)   |   607          701          452 (I)      473       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.066N     P=0.321      P=0.071N     P=0.118N   |  P=0.239      P=0.504      P=0.482N     P=0.279    |
|INCIDENTAL TUMOR       |  P=0.069N     P=0.455      P=0.051N     P=0.131N   |  P=0.291      P=0.443      P=0.436N     P=0.298    |
|LOGISTIC REGRESSION    |  P=0.080N     P=0.363      P=0.048N*    P=0.131N   |  P=0.284      P=0.492      P=0.387N     P=0.312    |
|COCHRAN-ARMITAGE       |  P=0.052N                                          |  P=0.411                                           |
|FISHER EXACT           |               P=0.221      P=0.238N     P=0.155N   |               P=0.174      P=0.528N     P=0.295    |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  20
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0PPM         1500 PPM     5000 PPM     15000  P  |   0PPM         1500 PPM     5000 PPM     15000  P  |
|                       |                                          PM        |                                          PM        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 20/70 (29%)  24/60 (40%)  21/61 (34%)  15/70 (21%) | 23/70 (33%)  23/61 (38%)  26/62 (42%)  21/70 (30%) |
|ADJUSTED (b)           |  40.8%        50.0%        43.5%        31.2%      |  46.8%        48.9%        54.8%        43.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/1 (0%)     0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/9 (0%)     0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 17/46 (37%)  20/44 (45%)  19/46 (41%)  13/46 (28%) | 16/42 (38%)  22/46 (48%)  17/38 (45%)  15/42 (36%) |
|FIRST INCIDENCE (DAYS) |   466          647          417          634       |   323          679          409          447       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.076N     P=0.229      P=0.499      P=0.217N   |  P=0.424N     P=0.426N     P=0.256      P=0.421N   |
|INCIDENTAL TUMOR       |  P=0.079N     P=0.204      P=0.451      P=0.179N   |  P=0.285N     P=0.443      P=0.446      P=0.404N   |
|LOGISTIC REGRESSION    |  P=0.079N     P=0.234      P=0.467      P=0.162N   |  P=0.329N     P=0.489N     P=0.280      P=0.385N   |
|COCHRAN-ARMITAGE       |  P=0.054N                                          |  P=0.268N                                          |
|FISHER EXACT           |               P=0.118      P=0.297      P=0.218N   |               P=0.346      P=0.185      P=0.428N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 49/70 (70%)  45/60 (75%)  40/61 (66%)  41/70 (59%) | 37/70 (53%)  37/61 (61%)  39/62 (63%)  36/70 (51%) |
|ADJUSTED (b)           |  94.1%        90.0%        79.9%        80.3%      |  75.4%        74.0%        77.7%        71.9%      |
|INTERIM SACRIFICE 1 (c)|  2/10 (20%)   1/1 (100%)   0/1 (0%)     0/9 (0%)   |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/9 (0%)     2/10 (20%) |  0/9 (0%)     0/10 (0%)    2/9 (22%)    0/9 (0%)   |
|TERMINAL (d)           | 43/46 (93%)  39/44 (89%)  36/46 (78%)  36/46 (78%) | 30/42 (71%)  33/46 (72%)  27/38 (71%)  28/42 (67%) |
|FIRST INCIDENCE (DAYS) |   276 (I)      276 (I)      417          452 (I)   |   323          679          409          447       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.055N     P=0.553      P=0.079N     P=0.072N   |  P=0.537      P=0.335N     P=0.243      P=0.488N   |
|INCIDENTAL TUMOR       |  P=0.037N*    P=0.552N     P=0.040N*    P=0.046N*  |  P=0.342N     P=0.581      P=0.455      P=0.446N   |
|LOGISTIC REGRESSION    |  P=0.062N     P=0.536N     P=0.046N*    P=0.059N   |  P=0.425N     P=0.386N     P=0.322      P=0.424N   |
|COCHRAN-ARMITAGE       |  P=0.037N*                                         |  P=0.289N                                          |
|FISHER EXACT           |               P=0.331      P=0.361N     P=0.108N   |               P=0.235      P=0.161      P=0.500N   |
|=================================================================================================================================|
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 02                                                 PAGE  21
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- MANGANESE SULFATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 (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):   276  452
          Female interim sacrifices(days): 276  452
 (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).