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TDMS Study 05085-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                      MANGANESE SULFATE                                  DATE: 09/11/94       
EXPERIMENT: 05085 TEST: 01                                                                                     TIME: 02:31:46       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 61143B       
PATHOLOGIST: J. TOFT                                                                                           CAS: 7785-87-7       
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Battelle Columbus                                      MANGANESE SULFATE                                  DATE: 09/11/94      
EXPERIMENT: 05085 TEST: 01                                                                                     TIME: 02:31:46      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 61143B      
PATHOLOGIST: J. TOFT                                                                                           CAS: 7785-87-7      
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                      MANGANESE SULFATE                                  DATE: 09/11/94       
EXPERIMENT: 05085 TEST: 01                                                                                     TIME: 02:31:46       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 61143B       
PATHOLOGIST: J. TOFT                                                                                           CAS: 7785-87-7       
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                       IN THE ANALYSIS OF THE STUDY OF MANGANESE SULFATE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Islets, Pancreatic            Carcinoma or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Skin: Subcutaneous Tissue     Fibrous Histiocytoma
                             Testes                        Adenoma
                             All Organs                    Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             All Organs                    Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   1
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/70 (20%)  17/70 (24%)  14/70 (20%)   6/70 (9%)  |  1/70 (1%)    0/61 (0%)    4/62 (6%)    1/68 (1%)  |
|ADJUSTED (b)           |  45.7%        52.7%        45.7%        31.8%      |   2.7%         0.0%         9.5%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  9/25 (36%)   3/17 (18%)   7/22 (32%)   0/7 (0%)   |  1/37 (3%)    0/37 (0%)    4/42 (10%)   1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   621          613          618          661       |   729 (T)      ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.232N     P=0.168      P=0.503      P=0.501N   |  P=0.552      P=0.500N     P=0.219      P=0.756    |
|INCIDENTAL TUMOR       |  P=0.002N**   P=0.499      P=0.551      P=0.038N*  |  P=0.552      P=0.500N     P=0.219      P=0.756    |
|LOGISTIC REGRESSION    |  P=0.003N**   P=0.299      P=0.576      P=0.077N   |  P=0.552      P=0.500N     P=0.219      P=0.756    |
|COCHRAN-ARMITAGE       |  P=0.013N*                                         |  P=0.574                                           |
|FISHER EXACT           |               P=0.342      P=0.584N     P=0.045N*  |               P=0.534N     P=0.147      P=0.745    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/70 (20%)  18/70 (26%)  16/70 (23%)   6/70 (9%)  |  2/70 (3%)    0/61 (0%)    4/62 (6%)    1/68 (1%)  |
|ADJUSTED (b)           |  45.7%        56.1%        53.0%        31.8%      |   5.1%         0.0%         9.5%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  9/25 (36%)   4/17 (24%)   9/22 (41%)   0/7 (0%)   |  1/37 (3%)    0/37 (0%)    4/42 (10%)   1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   621          613          618          661       |   694          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.246N     P=0.118      P=0.333      P=0.501N   |  P=0.572N     P=0.245N     P=0.389      P=0.504N   |
|INCIDENTAL TUMOR       |  P=0.003N**   P=0.391      P=0.361      P=0.038N*  |  P=0.529N     P=0.284N     P=0.334      P=0.460N   |
|LOGISTIC REGRESSION    |  P=0.003N**   P=0.226      P=0.393      P=0.077N   |  P=0.555N     P=0.251N     P=0.352      P=0.503N   |
|COCHRAN-ARMITAGE       |  P=0.011N*                                         |  P=0.548N                                          |
|FISHER EXACT           |               P=0.273      P=0.419      P=0.045N*  |               P=0.284N     P=0.284      P=0.511N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   2
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Astrocytoma Malignant                                                                                                       |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/69 (0%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   6.1%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   571          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.306N     P=0.282N     P=0.262N     P=0.371N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.296N     P=0.346N     P=0.299N     P=0.381N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.246N     P=0.246N     P=0.240N     P=0.247N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.242N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.252N     P=0.248N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/69 (0%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    1/68 (1%)  |
|ADJUSTED (b)           |   6.1%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   571          ---          ---          ---       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.306N     P=0.282N     P=0.262N     P=0.371N   |  P=0.205        (e)          (e)        P=0.495    |
|INCIDENTAL TUMOR       |  P=0.296N     P=0.346N     P=0.299N     P=0.381N   |  P=0.205        (e)          (e)        P=0.495    |
|LOGISTIC REGRESSION    |  P=0.246N     P=0.246N     P=0.240N     P=0.247N   |  P=0.205        (e)          (e)        P=0.495    |
|COCHRAN-ARMITAGE       |  P=0.242N                                          |  P=0.222                                           |
|FISHER EXACT           |               P=0.252N     P=0.248N     P=0.248N   |                 (e)          (e)        P=0.493    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   3
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    2/70 (3%)    2/70 (3%)    0/70 (0%)  |  5/69 (7%)    1/60 (2%)    6/58 (10%)   2/67 (3%)  |
|ADJUSTED (b)           |  12.0%         5.8%         6.5%         0.0%      |  12.7%         2.7%        14.8%         5.6%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/9 (11%)    1/9 (11%)    0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  3/25 (12%)   0/17 (0%)    1/22 (5%)    0/7 (0%)   |  4/37 (11%)   1/37 (3%)    5/39 (13%)   2/36 (6%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      437 (I)      437 (I)      ---       |   599          729 (T)      663          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.214N     P=0.619N     P=0.556N     P=0.411N   |  P=0.350N     P=0.110N     P=0.531      P=0.230N   |
|INCIDENTAL TUMOR       |  P=0.171N     P=0.550N     P=0.556N     P=0.411N   |  P=0.377N     P=0.120N     P=0.424      P=0.313N   |
|LOGISTIC REGRESSION    |  P=0.103N     P=0.509N     P=0.506N     P=0.411N   |  P=0.333N     P=0.119N     P=0.456      P=0.224N   |
|COCHRAN-ARMITAGE       |  P=0.099N                                          |  P=0.326N                                          |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.122N   |               P=0.140N     P=0.379      P=0.233N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    2/70 (3%)    4/70 (6%)    2/70 (3%)  |  0/69 (0%)    1/60 (2%)    1/58 (2%)    0/67 (0%)  |
|ADJUSTED (b)           |   4.9%         5.0%        14.9%         9.9%      |   0.0%         2.7%         2.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    2/22 (9%)    0/7 (0%)   |  0/37 (0%)    1/37 (3%)    0/39 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   571          613          659          655       |   ---          729 (T)      528          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.499      P=0.666N     P=0.322      P=0.646    |  P=0.547N     P=0.500      P=0.496        (e)      |
|INCIDENTAL TUMOR       |  P=0.464N     P=0.621      P=0.297      P=0.530N   |  P=0.543N     P=0.500        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.602      P=0.691      P=0.331      P=0.682    |  P=0.529N     P=0.500      P=0.456        (e)      |
|COCHRAN-ARMITAGE       |  P=0.593N                                          |  P=0.528N                                          |
|FISHER EXACT           |               P=0.690N     P=0.340      P=0.690N   |               P=0.465      P=0.457        (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   4
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/70 (7%)    4/70 (6%)    6/70 (9%)    2/70 (3%)  |  5/69 (7%)    2/60 (3%)    7/58 (12%)   2/67 (3%)  |
|ADJUSTED (b)           |  16.3%        10.5%        20.8%         9.9%      |  12.7%         5.4%        16.5%         5.6%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/9 (11%)    1/9 (11%)    0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  3/25 (12%)   0/17 (0%)    3/22 (14%)   0/7 (0%)   |  4/37 (11%)   2/37 (5%)    5/39 (13%)   2/36 (6%)  |
|FIRST INCIDENCE (DAYS) |   571          437 (I)      437 (I)      655       |   599          729 (T)      528          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.406N     P=0.570N     P=0.446      P=0.492N   |  P=0.294N     P=0.226N     P=0.409      P=0.230N   |
|INCIDENTAL TUMOR       |  P=0.196N     P=0.599N     P=0.428      P=0.306N   |  P=0.316N     P=0.241N     P=0.424      P=0.313N   |
|LOGISTIC REGRESSION    |  P=0.206N     P=0.510N     P=0.491      P=0.249N   |  P=0.278N     P=0.244N     P=0.320      P=0.224N   |
|COCHRAN-ARMITAGE       |  P=0.192N                                          |  P=0.269N                                          |
|FISHER EXACT           |               P=0.500N     P=0.500      P=0.221N   |               P=0.282N     P=0.267      P=0.233N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    3/69 (4%)    4/70 (6%)    3/69 (4%)  |  0/70 (0%)    0/60 (0%)    1/61 (2%)    0/68 (0%)  |
|ADJUSTED (b)           |   0.0%        11.5%        15.4%        20.5%      |   0.0%         0.0%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/17 (6%)    2/22 (9%)    1/7 (14%)  |  0/37 (0%)    0/37 (0%)    1/42 (2%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          613          701          631       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.100      P=0.102      P=0.062      P=0.053    |  P=0.795N       (e)        P=0.525        (e)      |
|INCIDENTAL TUMOR       |  P=0.258      P=0.104      P=0.071      P=0.086    |  P=0.795N       (e)        P=0.525        (e)      |
|LOGISTIC REGRESSION    |  P=0.221      P=0.116      P=0.060      P=0.100    |  P=0.795N       (e)        P=0.525        (e)      |
|COCHRAN-ARMITAGE       |  P=0.273                                           |  P=0.777N                                          |
|FISHER EXACT           |               P=0.120      P=0.060      P=0.120    |                 (e)        P=0.466        (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   5
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    3/69 (4%)    4/70 (6%)    4/69 (6%)  |  0/70 (0%)    0/60 (0%)    1/61 (2%)    0/68 (0%)  |
|ADJUSTED (b)           |   0.0%        11.5%        15.4%        23.3%      |   0.0%         0.0%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/17 (6%)    2/22 (9%)    1/7 (14%)  |  0/37 (0%)    0/37 (0%)    1/42 (2%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          613          701          631       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.036 *    P=0.102      P=0.062      P=0.026 *  |  P=0.795N       (e)        P=0.525        (e)      |
|INCIDENTAL TUMOR       |  P=0.148      P=0.104      P=0.071      P=0.067    |  P=0.795N       (e)        P=0.525        (e)      |
|LOGISTIC REGRESSION    |  P=0.104      P=0.116      P=0.060      P=0.051    |  P=0.795N       (e)        P=0.525        (e)      |
|COCHRAN-ARMITAGE       |  P=0.139                                           |  P=0.777N                                          |
|FISHER EXACT           |               P=0.120      P=0.060      P=0.058    |                 (e)        P=0.466        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    2/69 (3%)    0/70 (0%)    1/70 (1%)  |  0/70 (0%)    0/61 (0%)    1/62 (2%)    0/68 (0%)  |
|ADJUSTED (b)           |   4.0%         9.8%         0.0%         4.2%      |   0.0%         0.0%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    1/17 (6%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    1/42 (2%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      698          ---          687       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.640      P=0.398      P=0.525N     P=0.600    |  P=0.795N       (e)        P=0.525        (e)      |
|INCIDENTAL TUMOR       |  P=0.568N     P=0.494      P=0.525N     P=0.775    |  P=0.795N       (e)        P=0.525        (e)      |
|LOGISTIC REGRESSION    |  P=0.616N     P=0.472      P=0.525N     P=0.720    |  P=0.795N       (e)        P=0.525        (e)      |
|COCHRAN-ARMITAGE       |  P=0.549N                                          |  P=0.778N                                          |
|FISHER EXACT           |               P=0.495      P=0.500N     P=0.752N   |                 (e)        P=0.470        (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   6
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    2/69 (3%)    0/70 (0%)    1/70 (1%)  |  0/70 (0%)    0/61 (0%)    1/62 (2%)    0/68 (0%)  |
|ADJUSTED (b)           |   4.0%         9.8%         0.0%         4.2%      |   0.0%         0.0%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    1/17 (6%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    1/42 (2%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      698          ---          687       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.640      P=0.398      P=0.525N     P=0.600    |  P=0.795N       (e)        P=0.525        (e)      |
|INCIDENTAL TUMOR       |  P=0.568N     P=0.494      P=0.525N     P=0.775    |  P=0.795N       (e)        P=0.525        (e)      |
|LOGISTIC REGRESSION    |  P=0.616N     P=0.472      P=0.525N     P=0.720    |  P=0.795N       (e)        P=0.525        (e)      |
|COCHRAN-ARMITAGE       |  P=0.549N                                          |  P=0.778N                                          |
|FISHER EXACT           |               P=0.495      P=0.500N     P=0.752N   |                 (e)        P=0.470        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    3/70 (4%)    0/70 (0%)    0/70 (0%)  |  1/70 (1%)    1/61 (2%)    0/62 (0%)    2/68 (3%)  |
|ADJUSTED (b)           |   1.7%        12.5%         0.0%         0.0%      |   2.7%         2.7%         0.0%         5.6%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/17 (6%)    0/22 (0%)    0/7 (0%)   |  1/37 (3%)    1/37 (3%)    0/42 (0%)    2/36 (6%)  |
|FIRST INCIDENCE (DAYS) |   437 (I)      666          ---          ---       |   729 (T)      729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.215N     P=0.258      P=0.521N     P=0.545N   |  P=0.320      P=0.762      P=0.475N     P=0.490    |
|INCIDENTAL TUMOR       |  P=0.126N     P=0.390      P=0.521N     P=0.545N   |  P=0.320      P=0.762      P=0.475N     P=0.490    |
|LOGISTIC REGRESSION    |  P=0.154N     P=0.300      P=0.505N     P=0.497N   |  P=0.320      P=0.762      P=0.475N     P=0.490    |
|COCHRAN-ARMITAGE       |  P=0.151N                                          |  P=0.345                                           |
|FISHER EXACT           |               P=0.310      P=0.500N     P=0.500N   |               P=0.716      P=0.530N     P=0.489    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   7
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/70 (0%)    0/70 (0%)    1/70 (1%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   8.0%         0.0%         0.0%         3.7%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  2/25 (8%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          673       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.582      P=0.326N     P=0.266N     P=0.695    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.672      P=0.326N     P=0.266N     P=0.673N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.694      P=0.326N     P=0.266N     P=0.584N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.650N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.500N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    3/70 (4%)    0/70 (0%)    1/70 (1%)  |  1/70 (1%)    1/61 (2%)    0/62 (0%)    2/68 (3%)  |
|ADJUSTED (b)           |   9.5%        12.5%         0.0%         3.7%      |   2.7%         2.7%         0.0%         5.6%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  2/25 (8%)    1/17 (6%)    0/22 (0%)    0/7 (0%)   |  1/37 (3%)    1/37 (3%)    0/42 (0%)    2/36 (6%)  |
|FIRST INCIDENCE (DAYS) |   437 (I)      666          ---          673       |   729 (T)      729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.353N     P=0.555      P=0.145N     P=0.573N   |  P=0.320      P=0.762      P=0.475N     P=0.490    |
|INCIDENTAL TUMOR       |  P=0.200N     P=0.653N     P=0.145N     P=0.446N   |  P=0.320      P=0.762      P=0.475N     P=0.490    |
|LOGISTIC REGRESSION    |  P=0.207N     P=0.653      P=0.122N     P=0.318N   |  P=0.320      P=0.762      P=0.475N     P=0.490    |
|COCHRAN-ARMITAGE       |  P=0.195N                                          |  P=0.345                                           |
|FISHER EXACT           |               P=0.660N     P=0.122N     P=0.310N   |               P=0.716      P=0.530N     P=0.489    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   8
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    1/70 (1%)    2/70 (3%)  | 19/70 (27%)  16/61 (26%)  26/62 (42%)  16/68 (24%) |
|ADJUSTED (b)           |   4.0%         0.0%         3.1%        17.7%      |  45.9%        40.9%        57.7%        38.5%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    0/22 (0%)    1/7 (14%)  | 15/37 (41%)  14/37 (38%)  23/42 (55%)  11/36 (31%) |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          684          684       |   624          667          571          663       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.093      P=0.577N     P=0.754      P=0.212    |  P=0.390N     P=0.352N     P=0.246      P=0.358N   |
|INCIDENTAL TUMOR       |  P=0.208      P=0.577N     P=0.747N     P=0.327    |  P=0.347N     P=0.445N     P=0.104      P=0.370N   |
|LOGISTIC REGRESSION    |  P=0.185      P=0.577N     P=0.761      P=0.398    |  P=0.328N     P=0.420N     P=0.116      P=0.351N   |
|COCHRAN-ARMITAGE       |  P=0.232                                           |  P=0.321N                                          |
|FISHER EXACT           |               P=0.500N     P=0.752N     P=0.500    |               P=0.533N     P=0.054      P=0.385N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    1/70 (1%)    2/70 (3%)  | 19/70 (27%)  17/61 (28%)  26/62 (42%)  16/68 (24%) |
|ADJUSTED (b)           |   4.0%         0.0%         3.1%        17.7%      |  45.9%        43.5%        57.7%        38.5%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    0/22 (0%)    1/7 (14%)  | 15/37 (41%)  15/37 (41%)  23/42 (55%)  11/36 (31%) |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          684          684       |   624          667          571          663       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.093      P=0.577N     P=0.754      P=0.212    |  P=0.355N     P=0.430N     P=0.246      P=0.358N   |
|INCIDENTAL TUMOR       |  P=0.208      P=0.577N     P=0.747N     P=0.327    |  P=0.312N     P=0.529N     P=0.104      P=0.370N   |
|LOGISTIC REGRESSION    |  P=0.185      P=0.577N     P=0.761      P=0.398    |  P=0.293N     P=0.508N     P=0.116      P=0.351N   |
|COCHRAN-ARMITAGE       |  P=0.232                                           |  P=0.290N                                          |
|FISHER EXACT           |               P=0.500N     P=0.752N     P=0.500    |               P=0.540      P=0.054      P=0.385N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE   9
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    1/61 (2%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   8.0%         0.0%         0.0%         0.0%      |   0.0%         2.7%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  2/25 (8%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    1/37 (3%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          ---       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.386N     P=0.326N     P=0.266N     P=0.543N   |  P=0.583N     P=0.500        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.386N     P=0.326N     P=0.266N     P=0.543N   |  P=0.583N     P=0.500        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.386N     P=0.326N     P=0.266N     P=0.543N   |  P=0.583N     P=0.500        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.243N                                          |  P=0.570N                                          |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.248N   |               P=0.466        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/70 (0%)    1/70 (1%)    0/70 (0%)  |  0/70 (0%)    1/61 (2%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   8.0%         0.0%         4.5%         0.0%      |   0.0%         2.7%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  2/25 (8%)    0/17 (0%)    1/22 (5%)    0/7 (0%)   |  0/37 (0%)    1/37 (3%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          729 (T)      ---       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.491N     P=0.326N     P=0.545N     P=0.543N   |  P=0.583N     P=0.500        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.491N     P=0.326N     P=0.545N     P=0.543N   |  P=0.583N     P=0.500        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.491N     P=0.326N     P=0.545N     P=0.543N   |  P=0.583N     P=0.500        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.272N                                          |  P=0.570N                                          |
|FISHER EXACT           |               P=0.248N     P=0.500N     P=0.248N   |               P=0.466        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  10
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/69 (3%)    1/70 (1%)    0/69 (0%)  |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   0.0%         8.8%         3.6%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/17 (6%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          674          703          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.500N     P=0.201      P=0.515        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.326N     P=0.269      P=0.552        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.413N     P=0.229      P=0.498        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.380N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.245      P=0.500        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/70 (19%)  12/68 (18%)  15/70 (21%)  15/68 (22%) | 23/70 (33%)  17/61 (28%)  19/62 (31%)  22/67 (33%) |
|ADJUSTED (b)           |  39.0%        46.4%        43.0%        65.5%      |  53.1%        42.0%        44.2%        50.1%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     2/10 (20%) |
|TERMINAL (d)           |  7/25 (28%)   6/17 (35%)   6/22 (27%)   2/7 (29%)  | 17/37 (46%)  14/37 (38%)  18/42 (43%)  14/35 (40%) |
|FIRST INCIDENCE (DAYS) |   547          613          417          618       |   585          548          684          437 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.027 *    P=0.464      P=0.355      P=0.041 *  |  P=0.339      P=0.188N     P=0.154N     P=0.552N   |
|INCIDENTAL TUMOR       |  P=0.293      P=0.582      P=0.422      P=0.491    |  P=0.313      P=0.283N     P=0.291N     P=0.555    |
|LOGISTIC REGRESSION    |  P=0.331      P=0.563N     P=0.398      P=0.283    |  P=0.375      P=0.227N     P=0.253N     P=0.576N   |
|COCHRAN-ARMITAGE       |  P=0.305                                           |  P=0.434                                           |
|FISHER EXACT           |               P=0.532N     P=0.416      P=0.383    |               P=0.335N     P=0.467N     P=0.571N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  11
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/68 (0%)    1/70 (1%)    0/68 (0%)  |  0/70 (0%)    1/61 (2%)    0/62 (0%)    2/67 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.3%         0.0%      |   0.0%         2.7%         0.0%         4.2%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    1/37 (3%)    0/42 (0%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          557          ---       |   ---          729 (T)      ---          495       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.782N       (e)        P=0.487        (e)      |  P=0.151      P=0.500        (e)        P=0.240    |
|INCIDENTAL TUMOR       |  P=0.766N       (e)        P=0.419        (e)      |  P=0.064      P=0.500        (e)        P=0.128    |
|LOGISTIC REGRESSION    |  P=0.788N       (e)        P=0.500        (e)      |  P=0.157      P=0.500        (e)        P=0.229    |
|COCHRAN-ARMITAGE       |  P=0.789N                                          |  P=0.157                                           |
|FISHER EXACT           |                 (e)        P=0.500        (e)      |               P=0.466        (e)        P=0.237    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/70 (19%)  12/68 (18%)  16/70 (23%)  15/68 (22%) | 23/70 (33%)  18/61 (30%)  19/62 (31%)  24/67 (36%) |
|ADJUSTED (b)           |  39.0%        46.4%        44.3%        65.5%      |  53.1%        44.5%        44.2%        52.2%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     2/10 (20%) |
|TERMINAL (d)           |  7/25 (28%)   6/17 (35%)   6/22 (27%)   2/7 (29%)  | 17/37 (46%)  15/37 (41%)  18/42 (43%)  14/35 (40%) |
|FIRST INCIDENCE (DAYS) |   547          613          417          618       |   585          548          684          437 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.030 *    P=0.464      P=0.284      P=0.041 *  |  P=0.224      P=0.245N     P=0.154N     P=0.449    |
|INCIDENTAL TUMOR       |  P=0.299      P=0.582      P=0.323      P=0.491    |  P=0.173      P=0.358N     P=0.291N     P=0.415    |
|LOGISTIC REGRESSION    |  P=0.345      P=0.563N     P=0.286      P=0.283    |  P=0.205      P=0.296N     P=0.253N     P=0.349    |
|COCHRAN-ARMITAGE       |  P=0.310                                           |  P=0.307                                           |
|FISHER EXACT           |               P=0.532N     P=0.339      P=0.383    |               P=0.412N     P=0.467N     P=0.426    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  12
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    2/70 (3%)    0/70 (0%)  |  1/70 (1%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         7.5%         0.0%      |   2.7%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    1/22 (5%)    0/7 (0%)   |  1/37 (3%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          684          ---       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.685        (e)        P=0.233        (e)      |  P=0.479N     P=0.500N     P=0.475N     P=0.505N   |
|INCIDENTAL TUMOR       |  P=0.716N       (e)        P=0.253        (e)      |  P=0.479N     P=0.500N     P=0.475N     P=0.505N   |
|LOGISTIC REGRESSION    |  P=0.736N       (e)        P=0.235        (e)      |  P=0.479N     P=0.500N     P=0.475N     P=0.505N   |
|COCHRAN-ARMITAGE       |  P=0.697N                                          |  P=0.470N                                          |
|FISHER EXACT           |                 (e)        P=0.248        (e)      |               P=0.534N     P=0.530N     P=0.507N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    3/70 (4%)    0/70 (0%)  |  2/70 (3%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   4.0%         0.0%        11.1%         0.0%      |   5.4%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    1/22 (5%)    0/7 (0%)   |  2/37 (5%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          684          ---       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.659N     P=0.577N     P=0.291      P=0.752N   |  P=0.244N     P=0.238N     P=0.211N     P=0.244N   |
|INCIDENTAL TUMOR       |  P=0.459N     P=0.577N     P=0.329      P=0.752N   |  P=0.244N     P=0.238N     P=0.211N     P=0.244N   |
|LOGISTIC REGRESSION    |  P=0.520N     P=0.577N     P=0.301      P=0.752N   |  P=0.243N     P=0.238N     P=0.211N     P=0.244N   |
|COCHRAN-ARMITAGE       |  P=0.449N                                          |  P=0.241N                                          |
|FISHER EXACT           |               P=0.500N     P=0.310      P=0.500N   |               P=0.284N     P=0.279N     P=0.255N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  13
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    1/70 (1%)    4/70 (6%)    2/70 (3%)  |  2/70 (3%)    2/61 (3%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |  10.7%         5.9%        13.6%        18.0%      |   5.4%         5.2%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    1/17 (6%)    1/22 (5%)    0/7 (0%)   |  2/37 (5%)    1/37 (3%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   691          729 (T)      635          713       |   729 (T)      718          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.396      P=0.403N     P=0.494      P=0.567    |  P=0.123N     P=0.691N     P=0.211N     P=0.244N   |
|INCIDENTAL TUMOR       |  P=0.448N     P=0.241N     P=0.531      P=0.239N   |  P=0.104N     P=0.658      P=0.211N     P=0.244N   |
|LOGISTIC REGRESSION    |  P=0.589      P=0.321N     P=0.493      P=0.619N   |  P=0.118N     P=0.683      P=0.211N     P=0.244N   |
|COCHRAN-ARMITAGE       |  P=0.560N                                          |  P=0.122N                                          |
|FISHER EXACT           |               P=0.310N     P=0.500      P=0.500N   |               P=0.637      P=0.279N     P=0.255N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/70 (1%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    2/61 (3%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   2.0%         1.7%         0.0%         0.0%      |   0.0%         5.4%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    2/37 (5%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   495          333          ---          ---       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.304N     P=0.751      P=0.504N     P=0.500N   |  P=0.374N     P=0.238        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.278N     P=0.716N     P=0.305N     P=0.500N   |  P=0.374N     P=0.238        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.304N     P=0.753N     P=0.501N     P=0.496N   |  P=0.373N     P=0.238        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.303N                                          |  P=0.365N                                          |
|FISHER EXACT           |               P=0.752N     P=0.500N     P=0.500N   |               P=0.215        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  14
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrous Histiocytoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    0/70 (0%)    2/70 (3%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         2.9%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          268       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.043 *      (e)          (e)        P=0.243    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.080        (e)          (e)        P=0.309    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.024 *      (e)          (e)        P=0.184    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.042 *                                         |    (e)                                             |
|FISHER EXACT           |                 (e)          (e)        P=0.248    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/70 (1%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   6.9%         4.3%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   673          711          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.235N     P=0.562N     P=0.257N     P=0.397N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.131N     P=0.375N     P=0.224N     P=0.225N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.186N     P=0.512N     P=0.240N     P=0.270N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.170N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  15
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    2/70 (3%)    1/70 (1%)    1/70 (1%)  |  0/70 (0%)    3/61 (5%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   8.8%         6.0%         2.6%         6.3%      |   0.0%         7.7%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    2/37 (5%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   495          333          618          713       |   ---          667          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.345N     P=0.555N     P=0.322N     P=0.479N   |  P=0.255N     P=0.120        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.187N     P=0.369N     P=0.247N     P=0.219N   |  P=0.218N     P=0.099        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.268N     P=0.501N     P=0.308N     P=0.321N   |  P=0.253N     P=0.110        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.264N                                          |  P=0.252N                                          |
|FISHER EXACT           |               P=0.500N     P=0.310N     P=0.310N   |               P=0.098        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    2/61 (3%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   8.8%         6.0%         0.0%         0.0%      |   0.0%         5.4%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    2/37 (5%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   495          333          ---          ---       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.099N     P=0.555N     P=0.135N     P=0.207N   |  P=0.374N     P=0.238        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.053N     P=0.369N     P=0.065N     P=0.111N   |  P=0.374N     P=0.238        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.073N     P=0.501N     P=0.123N     P=0.126N   |  P=0.373N     P=0.238        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.073N                                          |  P=0.365N                                          |
|FISHER EXACT           |               P=0.500N     P=0.122N     P=0.122N   |               P=0.215        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  16
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    1/70 (1%)    1/70 (1%)  |  0/70 (0%)    0/61 (0%)    2/62 (3%)    0/68 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         3.3%        10.0%      |   0.0%         0.0%         4.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    2/42 (5%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          698          726       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.185        (e)        P=0.521      P=0.310    |  P=0.708N       (e)        P=0.267        (e)      |
|INCIDENTAL TUMOR       |  P=0.471        (e)        P=0.552      P=0.705    |  P=0.708N       (e)        P=0.267        (e)      |
|LOGISTIC REGRESSION    |  P=0.252        (e)        P=0.497      P=0.360    |  P=0.708N       (e)        P=0.267        (e)      |
|COCHRAN-ARMITAGE       |  P=0.303                                           |  P=0.688N                                          |
|FISHER EXACT           |                 (e)        P=0.500      P=0.500    |                 (e)        P=0.219        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 48/70 (69%)  44/70 (63%)  42/70 (60%)  43/70 (61%) |                                                    |
|ADJUSTED (b)           | 100.0%        97.7%       100.0%        97.6%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   2/9 (22%)    0/9 (0%)     2/8 (25%)  |                                                    |
|TERMINAL (d)           | 25/25 (100%) 16/17 (94%)  22/22 (100%)  6/7 (86%)  |                                                    |
|FIRST INCIDENCE (DAYS) |   437 (I)      437 (I)      481          437 (I)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.005 **   P=0.295      P=0.388N     P=0.010 ** |                                                    |
|INCIDENTAL TUMOR       |  P=0.348N     P=0.318N     P=0.078N     P=0.337N   |                                                    |
|LOGISTIC REGRESSION    |  P=0.210N     P=0.284N     P=0.122N     P=0.197N   |                                                    |
|COCHRAN-ARMITAGE       |  P=0.295N                                          |                                                    |
|FISHER EXACT           |               P=0.297N     P=0.189N     P=0.239N   |                                                    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  17
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thymus                                                                                                                           |
|     Thymoma Benign                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    0/66 (0%)    0/68 (0%)    0/63 (0%)  |  2/66 (3%)    0/59 (0%)    1/58 (2%)    1/65 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   5.9%         0.0%         2.6%         2.9%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/23 (0%)    0/16 (0%)    0/21 (0%)    0/6 (0%)   |  2/34 (6%)    0/37 (0%)    1/38 (3%)    1/34 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   729 (T)      ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.634N     P=0.220N     P=0.461N     P=0.500N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.634N     P=0.220N     P=0.461N     P=0.500N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.634N     P=0.220N     P=0.461N     P=0.500N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.606N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.277N     P=0.549N     P=0.506N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/70 (9%)    8/67 (12%)   7/70 (10%)   4/69 (6%)  |  8/70 (11%)   7/61 (11%)   6/61 (10%)   8/68 (12%) |
|ADJUSTED (b)           |  19.6%        29.7%        22.4%        12.9%      |  19.8%        18.9%        13.9%        21.3%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  4/25 (16%)   3/17 (18%)   3/22 (14%)   0/7 (0%)   |  6/37 (16%)   7/37 (19%)   5/42 (12%)   7/36 (19%) |
|FIRST INCIDENCE (DAYS) |   495          451          519          631       |   599          729 (T)      663          684       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.507N     P=0.250      P=0.447      P=0.583    |  P=0.486      P=0.511N     P=0.314N     P=0.589    |
|INCIDENTAL TUMOR       |  P=0.260N     P=0.347      P=0.499      P=0.566N   |  P=0.443      P=0.561N     P=0.435N     P=0.446    |
|LOGISTIC REGRESSION    |  P=0.235N     P=0.344      P=0.491      P=0.415N   |  P=0.518      P=0.551N     P=0.390N     P=0.597    |
|COCHRAN-ARMITAGE       |  P=0.209N                                          |  P=0.533                                           |
|FISHER EXACT           |               P=0.356      P=0.500      P=0.381N   |               P=0.603      P=0.498N     P=0.580    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  18
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/67 (0%)    0/70 (0%)    1/69 (1%)  |  1/70 (1%)    2/61 (3%)    1/61 (2%)    0/68 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         1.8%      |   2.7%         5.4%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     1/8 (13%)  |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  1/37 (3%)    2/37 (5%)    1/42 (2%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          437 (I)   |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.187        (e)          (e)        P=0.455    |  P=0.234N     P=0.500      P=0.733N     P=0.505N   |
|INCIDENTAL TUMOR       |  P=0.187        (e)          (e)        P=0.455    |  P=0.234N     P=0.500      P=0.733N     P=0.505N   |
|LOGISTIC REGRESSION    |  P=0.219        (e)          (e)        P=0.502    |  P=0.234N     P=0.500      P=0.733N     P=0.505N   |
|COCHRAN-ARMITAGE       |  P=0.214                                           |  P=0.229N                                          |
|FISHER EXACT           |                 (e)          (e)        P=0.496    |               P=0.448      P=0.716      P=0.507N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/70 (9%)    8/67 (12%)   7/70 (10%)   5/69 (7%)  |  9/70 (13%)   9/61 (15%)   7/61 (11%)   8/68 (12%) |
|ADJUSTED (b)           |  19.6%        29.7%        22.4%        14.4%      |  22.4%        24.3%        16.2%        21.3%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     1/8 (13%)  |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  4/25 (16%)   3/17 (18%)   3/22 (14%)   0/7 (0%)   |  7/37 (19%)   9/37 (24%)   6/42 (14%)   7/36 (19%) |
|FIRST INCIDENCE (DAYS) |   495          451          519          437 (I)   |   599          729 (T)      663          684       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.492      P=0.250      P=0.447      P=0.435    |  P=0.472N     P=0.593      P=0.311N     P=0.519N   |
|INCIDENTAL TUMOR       |  P=0.402N     P=0.347      P=0.499      P=0.558    |  P=0.511N     P=0.548      P=0.425N     P=0.556    |
|LOGISTIC REGRESSION    |  P=0.354N     P=0.344      P=0.491      P=0.536N   |  P=0.434N     P=0.548      P=0.392N     P=0.511N   |
|COCHRAN-ARMITAGE       |  P=0.324N                                          |  P=0.422N                                          |
|FISHER EXACT           |               P=0.356      P=0.500      P=0.510N   |               P=0.474      P=0.512N     P=0.526N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  19
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/67 (1%)    1/70 (1%)    3/69 (4%)  |  0/70 (0%)    0/61 (0%)    0/61 (0%)    1/68 (1%)  |
|ADJUSTED (b)           |   3.0%         3.3%         2.6%        12.7%      |   0.0%         0.0%         0.0%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   673          682          621          527       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.119      P=0.757      P=0.757      P=0.227    |  P=0.205        (e)          (e)        P=0.495    |
|INCIDENTAL TUMOR       |  P=0.322      P=0.600N     P=0.748      P=0.583    |  P=0.205        (e)          (e)        P=0.495    |
|LOGISTIC REGRESSION    |  P=0.146      P=0.749      P=0.760      P=0.283    |  P=0.205        (e)          (e)        P=0.495    |
|COCHRAN-ARMITAGE       |  P=0.158                                           |  P=0.222                                           |
|FISHER EXACT           |               P=0.741      P=0.752N     P=0.304    |                 (e)          (e)        P=0.493    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/67 (3%)    0/70 (0%)    0/69 (0%)  |  1/70 (1%)    1/61 (2%)    1/61 (2%)    0/68 (0%)  |
|ADJUSTED (b)           |   0.0%         8.0%         0.0%         0.0%      |   2.7%         2.7%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  1/37 (3%)    1/37 (3%)    1/42 (2%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          684          ---          ---       |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.454N     P=0.214        (e)          (e)      |  P=0.327N     P=0.762      P=0.733N     P=0.505N   |
|INCIDENTAL TUMOR       |  P=0.242N     P=0.400        (e)          (e)      |  P=0.327N     P=0.762      P=0.733N     P=0.505N   |
|LOGISTIC REGRESSION    |  P=0.393N     P=0.223        (e)          (e)      |  P=0.327N     P=0.762      P=0.733N     P=0.505N   |
|COCHRAN-ARMITAGE       |  P=0.369N                                          |  P=0.319N                                          |
|FISHER EXACT           |               P=0.237        (e)          (e)      |               P=0.716      P=0.716      P=0.507N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  20
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    3/67 (4%)    1/70 (1%)    3/69 (4%)  |  1/70 (1%)    1/61 (2%)    1/61 (2%)    1/68 (1%)  |
|ADJUSTED (b)           |   3.0%        11.0%         2.6%        12.7%      |   2.7%         2.7%         2.4%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  1/37 (3%)    1/37 (3%)    1/42 (2%)    1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   673          682          621          527       |   729 (T)      729 (T)      729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.253      P=0.285      P=0.757      P=0.227    |  P=0.661      P=0.762      P=0.733N     P=0.756    |
|INCIDENTAL TUMOR       |  P=0.602      P=0.574      P=0.748      P=0.583    |  P=0.661      P=0.762      P=0.733N     P=0.756    |
|LOGISTIC REGRESSION    |  P=0.322      P=0.283      P=0.760      P=0.283    |  P=0.661      P=0.762      P=0.733N     P=0.756    |
|COCHRAN-ARMITAGE       |  P=0.346                                           |  P=0.655N                                          |
|FISHER EXACT           |               P=0.293      P=0.752N     P=0.304    |               P=0.716      P=0.716      P=0.745    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 13/70 (19%)   7/61 (11%)   8/62 (13%)   7/68 (10%) |
|ADJUSTED (b)           |                                                    |  34.1%        17.5%        17.3%        18.9%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/9 (0%)     2/8 (25%)    0/10 (0%)  |
|TERMINAL (d)           |                                                    | 12/37 (32%)   5/37 (14%)   6/42 (14%)   6/36 (17%) |
|FIRST INCIDENCE (DAYS) |                                                    |   694          451          437 (I)      715       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.207N     P=0.109N     P=0.115N     P=0.115N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.165N     P=0.074N     P=0.131N     P=0.095N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.186N     P=0.135N     P=0.178N     P=0.099N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.179N                                          |
|FISHER EXACT           |                                                    |               P=0.189N     P=0.259N     P=0.127N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  21
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 13/70 (19%)   8/61 (13%)   8/62 (13%)   7/68 (10%) |
|ADJUSTED (b)           |                                                    |  34.1%        18.9%        17.3%        18.9%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/9 (0%)     2/8 (25%)    0/10 (0%)  |
|TERMINAL (d)           |                                                    | 12/37 (32%)   5/37 (14%)   6/42 (14%)   6/36 (17%) |
|FIRST INCIDENCE (DAYS) |                                                    |   694          396          437 (I)      715       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.178N     P=0.170N     P=0.115N     P=0.115N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.140N     P=0.074N     P=0.131N     P=0.095N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.159N     P=0.211N     P=0.178N     P=0.099N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.152N                                          |
|FISHER EXACT           |                                                    |               P=0.272N     P=0.259N     P=0.127N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/70 (1%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   4.5%         2.1%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    0/22 (0%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   437 (I)      451          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.182N     P=0.510N     P=0.255N     P=0.268N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.135N     P=0.429N     P=0.222N     P=0.152N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.168N     P=0.494N     P=0.238N     P=0.236N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.170N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  22
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/70 (1%)    1/70 (1%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   4.5%         2.1%         4.5%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/17 (0%)    1/22 (5%)    0/7 (0%)   |  0/37 (0%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   437 (I)      451          729 (T)      ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.247N     P=0.510N     P=0.530N     P=0.268N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.195N     P=0.429N     P=0.497N     P=0.152N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.194N     P=0.494N     P=0.501N     P=0.236N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.194N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/70 (46%)  31/70 (44%)  30/70 (43%)  25/70 (36%) | 19/70 (27%)  21/61 (34%)  26/62 (42%)  18/68 (26%) |
|ADJUSTED (b)           |  79.0%        90.5%        77.1%        93.6%      |  42.5%        51.2%        54.1%        43.6%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           | 17/25 (68%)  14/17 (82%)  14/22 (64%)   6/7 (86%)  | 12/37 (32%)  17/37 (46%)  20/42 (48%)  13/36 (36%) |
|FIRST INCIDENCE (DAYS) |   526          532          481          498       |   599          609          528          527       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.126      P=0.240      P=0.557      P=0.130    |  P=0.400N     P=0.398      P=0.244      P=0.527N   |
|INCIDENTAL TUMOR       |  P=0.246N     P=0.495      P=0.468N     P=0.497N   |  P=0.384N     P=0.230      P=0.064      P=0.581N   |
|LOGISTIC REGRESSION    |  P=0.058N     P=0.535N     P=0.527N     P=0.091N   |  P=0.405N     P=0.144      P=0.051      P=0.539    |
|COCHRAN-ARMITAGE       |  P=0.116N                                          |  P=0.320N                                          |
|FISHER EXACT           |               P=0.500N     P=0.432N     P=0.151N   |               P=0.238      P=0.054      P=0.541N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  23
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    2/70 (3%)    0/70 (0%)    1/70 (1%)  |  0/70 (0%)    0/61 (0%)    0/62 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |   5.9%         9.3%         0.0%        14.3%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/8 (0%)   |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/17 (0%)    0/22 (0%)    1/7 (14%)  |  0/37 (0%)    0/37 (0%)    0/42 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   456          717          ---          729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.618N     P=0.612      P=0.256N     P=0.715    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.388N     P=0.599N     P=0.149N     P=0.717    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.400N     P=0.688      P=0.238N     P=0.511N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.382N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.690N     P=0.248N     P=0.500N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 53/70 (76%)  48/70 (69%)  49/70 (70%)  49/70 (70%) | 40/70 (57%)  36/61 (59%)  45/62 (73%)  38/68 (56%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  88.8%        79.9%        93.7%        80.7%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  4/10 (40%)   3/9 (33%)    1/9 (11%)    2/8 (25%)  |  0/10 (0%)    0/9 (0%)     2/8 (25%)    2/10 (20%) |
|TERMINAL (d)           | 25/25 (100%) 17/17 (100%) 22/22 (100%)  7/7 (100%) | 32/37 (86%)  28/37 (76%)  39/42 (93%)  27/36 (75%) |
|FIRST INCIDENCE (DAYS) |   437 (I)      437 (I)      417          437 (I)   |   585          451          437 (I)      437 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.003 **   P=0.337      P=0.522N     P=0.008 ** |  P=0.532      P=0.319N     P=0.527      P=0.472N   |
|INCIDENTAL TUMOR       |  P=0.408N     P=0.198N     P=0.113N     P=0.297N   |  P=0.532      P=0.458N     P=0.125      P=0.581    |
|LOGISTIC REGRESSION    |  P=0.303N     P=0.227N     P=0.247N     P=0.233N   |  P=0.489N     P=0.478N     P=0.105      P=0.500N   |
|COCHRAN-ARMITAGE       |  P=0.388N                                          |  P=0.399N                                          |
|FISHER EXACT           |               P=0.226N     P=0.284N     P=0.284N   |               P=0.485      P=0.047 *    P=0.509N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  24
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- MANGANESE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        1500 PPM     5000 PPM     15000  P  |   0 PPM        1500 PPM     5000 PPM     15000     |
|                       |                                          PM        |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 39/70 (56%)  38/70 (54%)  34/70 (49%)  31/70 (44%) | 24/70 (34%)  26/61 (43%)  30/62 (48%)  22/68 (32%) |
|ADJUSTED (b)           |  83.9%        94.7%        83.8%        94.5%      |  51.7%        60.1%        61.2%        49.5%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/9 (0%)     0/9 (0%)     1/8 (13%)  |  0/10 (0%)    0/9 (0%)     0/8 (0%)     0/10 (0%)  |
|TERMINAL (d)           | 18/25 (72%)  15/17 (88%)  16/22 (73%)   6/7 (86%)  | 15/37 (41%)  20/37 (54%)  23/42 (55%)  14/36 (39%) |
|FIRST INCIDENCE (DAYS) |   269          333          481          268       |   585          396          528          495       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.134      P=0.236      P=0.409N     P=0.149    |  P=0.337N     P=0.396      P=0.333      P=0.460N   |
|INCIDENTAL TUMOR       |  P=0.145N     P=0.516      P=0.267N     P=0.314N   |  P=0.359N     P=0.338      P=0.068      P=0.508N   |
|LOGISTIC REGRESSION    |  P=0.082N     P=0.566N     P=0.246N     P=0.130N   |  P=0.365N     P=0.297      P=0.062      P=0.552    |
|COCHRAN-ARMITAGE       |  P=0.088N                                          |  P=0.251N                                          |
|FISHER EXACT           |               P=0.500N     P=0.249N     P=0.118N   |               P=0.212      P=0.071      P=0.476N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 55/70 (79%)  50/70 (71%)  50/70 (71%)  54/70 (77%) | 45/70 (64%)  47/61 (77%)  51/62 (82%)  44/68 (65%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  91.8%        95.9%       100.0%        87.9%      |
|INTERIM SACRIFICE 1 (c)|  0/8 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/2 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  4/10 (40%)   3/9 (33%)    1/9 (11%)    3/8 (38%)  |  0/10 (0%)    0/9 (0%)     2/8 (25%)    2/10 (20%) |
|TERMINAL (d)           | 25/25 (100%) 17/17 (100%) 22/22 (100%)  7/7 (100%) | 33/37 (89%)  35/37 (95%)  42/42 (100%) 30/36 (83%) |
|FIRST INCIDENCE (DAYS) |   269          333          417          268       |   585          396          437 (I)      437 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.001 **   P=0.342      P=0.472N     P=0.004 ** |  P=0.443N     P=0.369      P=0.467      P=0.549N   |
|INCIDENTAL TUMOR       |  P=0.318      P=0.209N     P=0.110N     P=0.632    |  P=0.497N     P=0.249      P=0.009 **   P=0.605    |
|LOGISTIC REGRESSION    |  P=0.339      P=0.243N     P=0.129N     P=0.566    |  P=0.457N     P=0.097      P=0.011 *    P=0.467    |
|COCHRAN-ARMITAGE       |  P=0.438                                           |  P=0.259N                                          |
|FISHER EXACT           |               P=0.218N     P=0.218N     P=0.500N   |               P=0.080      P=0.016 *    P=0.550    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05085 TEST: 01                                                 PAGE  25
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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):   275  437
          Female interim sacrifices(days): 275  437
 (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).