National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/3810

TDMS Study 05087-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                        TRIAMTERENE                                      DATE: 09/11/94       
EXPERIMENT: 05087 TEST: 01                                                                                     TIME: 11:29:42       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 56042B       
PATHOLOGIST: M. RYAN                         S. EUSTIS                                                         CAS: 396-01-0        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Battelle Columbus                                        TRIAMTERENE                                      DATE: 09/11/94      
EXPERIMENT: 05087 TEST: 01                                                                                     TIME: 11:29:42      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 56042B      
PATHOLOGIST: M. RYAN                         S. EUSTIS                                                         CAS: 396-01-0       
 
 
 
 
 
                                                    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                                        TRIAMTERENE                                      DATE: 09/11/94       
EXPERIMENT: 05087 TEST: 01                                                                                     TIME: 11:29:42       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 56042B       
PATHOLOGIST: M. RYAN                         S. EUSTIS                                                         CAS: 396-01-0        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                          IN THE ANALYSIS OF THE STUDY OF TRIAMTERENE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Adenoma
                             Testes                        Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Adenoma
                             Uterus                        Leiomyoma
                             All Organs                    Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   1
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/60 (2%)    0/61 (0%)    0/70 (0%)  |  2/70 (3%)    0/61 (0%)    1/63 (2%)    0/70 (0%)  |
|ADJUSTED (b)           |   3.6%         4.0%         0.0%         0.0%      |   6.9%         0.0%         2.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/25 (4%)    0/19 (0%)    0/27 (0%)  |  2/29 (7%)    0/34 (0%)    1/34 (3%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   719          729 (T)      ---          ---       |   729 (T)      ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.244N     P=0.752      P=0.557N     P=0.507N   |  P=0.186N     P=0.204N     P=0.444N     P=0.238N   |
|INCIDENTAL TUMOR       |  P=0.221N     P=0.743N     P=0.388N     P=0.484N   |  P=0.186N     P=0.204N     P=0.444N     P=0.238N   |
|LOGISTIC REGRESSION    |  P=0.234N     P=0.764      P=0.509N     P=0.488N   |  P=0.186N     P=0.204N     P=0.444N     P=0.238N   |
|COCHRAN-ARMITAGE       |  P=0.237N                                          |  P=0.188N                                          |
|FISHER EXACT           |               P=0.712      P=0.534N     P=0.500N   |               P=0.284N     P=0.540N     P=0.248N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/70 (14%)  11/60 (18%)   8/61 (13%)   7/69 (10%) |  0/70 (0%)    1/61 (2%)    0/63 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |  33.8%        38.1%        29.0%        25.7%      |   0.0%         2.9%         0.0%         3.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  7/25 (28%)   8/25 (32%)   3/19 (16%)   6/26 (23%) |  0/29 (0%)    1/34 (3%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      674          668          712       |   ---          729 (T)      ---          707       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.181N     P=0.502      P=0.546N     P=0.269N   |  P=0.394      P=0.532        (e)        P=0.500    |
|INCIDENTAL TUMOR       |  P=0.162N     P=0.538      P=0.340N     P=0.260N   |  P=0.376      P=0.532        (e)        P=0.438    |
|LOGISTIC REGRESSION    |  P=0.164N     P=0.561      P=0.346N     P=0.256N   |  P=0.388      P=0.532        (e)        P=0.491    |
|COCHRAN-ARMITAGE       |  P=0.191N                                          |  P=0.414                                           |
|FISHER EXACT           |               P=0.349      P=0.526N     P=0.314N   |               P=0.466        (e)        P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   2
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    2/60 (3%)    0/61 (0%)    0/69 (0%)  |  1/70 (1%)    1/61 (2%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   4.0%         8.0%         0.0%         0.0%      |   2.2%         2.9%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    2/25 (8%)    0/19 (0%)    0/26 (0%)  |  0/29 (0%)    1/34 (3%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      ---          ---       |   573          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.193N     P=0.500      P=0.555N     P=0.492N   |  P=0.237N     P=0.738N     P=0.496N     P=0.504N   |
|INCIDENTAL TUMOR       |  P=0.193N     P=0.500      P=0.555N     P=0.492N   |  P=0.225N     P=0.743N     P=0.557N     P=0.455N   |
|LOGISTIC REGRESSION    |  P=0.193N     P=0.500      P=0.555N     P=0.492N   |  P=0.237N     P=0.752      P=0.529N     P=0.500N   |
|COCHRAN-ARMITAGE       |  P=0.191N                                          |  P=0.236N                                          |
|FISHER EXACT           |               P=0.442      P=0.534N     P=0.504N   |               P=0.716      P=0.526N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/70 (16%)  12/60 (20%)   8/61 (13%)   7/69 (10%) |  1/70 (1%)    2/61 (3%)    0/63 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |  37.5%        41.8%        29.0%        25.7%      |   2.2%         5.9%         0.0%         3.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  8/25 (32%)   9/25 (36%)   3/19 (16%)   6/26 (23%) |  0/29 (0%)    2/34 (6%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      674          668          712       |   573          729 (T)      ---          707       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.117N     P=0.502      P=0.460N     P=0.191N   |  P=0.512N     P=0.542      P=0.496N     P=0.758    |
|INCIDENTAL TUMOR       |  P=0.100N     P=0.538      P=0.264N     P=0.183N   |  P=0.508N     P=0.537      P=0.557N     P=0.753    |
|LOGISTIC REGRESSION    |  P=0.101N     P=0.564      P=0.257N     P=0.180N   |  P=0.509N     P=0.497      P=0.529N     P=0.759    |
|COCHRAN-ARMITAGE       |  P=0.126N                                          |  P=0.490N                                          |
|FISHER EXACT           |               P=0.341      P=0.433N     P=0.235N   |               P=0.448      P=0.526N     P=0.752N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   3
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    2/60 (3%)    5/61 (8%)    3/69 (4%)  |  3/62 (5%)    3/60 (5%)    4/63 (6%)    3/68 (4%)  |
|ADJUSTED (b)           |   6.8%         6.1%        13.1%        11.1%      |  11.5%         8.3%        10.5%         9.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/25 (4%)    1/19 (5%)    3/27 (11%) |  3/26 (12%)   2/34 (6%)    2/34 (6%)    2/28 (7%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      610          456 (I)      729 (T)   |   729 (T)      708          619          541       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.503      P=0.488N     P=0.356      P=0.644N   |  P=0.555      P=0.540N     P=0.619      P=0.636N   |
|INCIDENTAL TUMOR       |  P=0.517      P=0.413N     P=0.440      P=0.644N   |  P=0.534N     P=0.564N     P=0.595      P=0.581N   |
|LOGISTIC REGRESSION    |  P=0.496      P=0.562N     P=0.261      P=0.647N   |  P=0.578N     P=0.564N     P=0.593      P=0.625N   |
|COCHRAN-ARMITAGE       |  P=0.493                                           |  P=0.535N                                          |
|FISHER EXACT           |               P=0.573N     P=0.285      P=0.653    |               P=0.644      P=0.509      P=0.615N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    2/60 (3%)    5/61 (8%)    3/69 (4%)  |  4/62 (6%)    3/60 (5%)    4/63 (6%)    3/68 (4%)  |
|ADJUSTED (b)           |   6.8%         6.1%        13.1%        11.1%      |  14.4%         8.3%        10.5%         9.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/25 (4%)    1/19 (5%)    3/27 (11%) |  3/26 (12%)   2/34 (6%)    2/34 (6%)    2/28 (7%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      610          456 (I)      729 (T)   |   715          708          619          541       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.503      P=0.488N     P=0.356      P=0.644N   |  P=0.469N     P=0.369N     P=0.524N     P=0.475N   |
|INCIDENTAL TUMOR       |  P=0.517      P=0.413N     P=0.440      P=0.644N   |  P=0.401N     P=0.411N     P=0.562N     P=0.419N   |
|LOGISTIC REGRESSION    |  P=0.496      P=0.562N     P=0.261      P=0.647N   |  P=0.440N     P=0.390N     P=0.547N     P=0.456N   |
|COCHRAN-ARMITAGE       |  P=0.493                                           |  P=0.403N                                          |
|FISHER EXACT           |               P=0.573N     P=0.285      P=0.653    |               P=0.518N     P=0.632N     P=0.448N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   4
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ear                                                                                                                              |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   6.7%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/25 (0%)    0/19 (0%)    0/27 (0%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   653          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.114N     P=0.234N     P=0.260N     P=0.223N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.105N     P=0.223N     P=0.205N     P=0.223N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.109N     P=0.225N     P=0.226N     P=0.222N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.118N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.288N     P=0.284N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/60 (2%)    5/61 (8%)    1/69 (1%)  |  3/70 (4%)    0/61 (0%)    2/63 (3%)    1/70 (1%)  |
|ADJUSTED (b)           |   6.5%         4.0%        14.8%         2.1%      |   9.0%         0.0%         5.9%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    1/25 (4%)    1/19 (5%)    0/27 (0%)  |  2/29 (7%)    0/34 (0%)    2/34 (6%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   624          729 (T)      572          522       |   660          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.490N     P=0.494N     P=0.221      P=0.469N   |  P=0.353N     P=0.105N     P=0.444N     P=0.322N   |
|INCIDENTAL TUMOR       |  P=0.491N     P=0.406N     P=0.412      P=0.479N   |  P=0.359N     P=0.126N     P=0.478N     P=0.334N   |
|LOGISTIC REGRESSION    |  P=0.481N     P=0.480N     P=0.232      P=0.489N   |  P=0.359N     P=0.114N     P=0.486N     P=0.323N   |
|COCHRAN-ARMITAGE       |  P=0.513N                                          |  P=0.330N                                          |
|FISHER EXACT           |               P=0.558N     P=0.167      P=0.505N   |               P=0.150N     P=0.550N     P=0.310N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   5
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    6/60 (10%)   4/61 (7%)    3/69 (4%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    2/70 (3%)  |
|ADJUSTED (b)           |   0.0%        20.9%        15.6%         9.3%      |   0.0%         0.0%         0.0%         6.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    4/25 (16%)   2/19 (11%)   2/27 (7%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    2/29 (7%)  |
|FIRST INCIDENCE (DAYS) |   ---          610          668          508       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.368      P=0.020 *    P=0.054      P=0.140    |  P=0.039 *      (e)          (e)        P=0.238    |
|INCIDENTAL TUMOR       |  P=0.356      P=0.028 *    P=0.078      P=0.107    |  P=0.039 *      (e)          (e)        P=0.238    |
|LOGISTIC REGRESSION    |  P=0.361      P=0.020 *    P=0.067      P=0.130    |  P=0.039 *      (e)          (e)        P=0.238    |
|COCHRAN-ARMITAGE       |  P=0.347                                           |  P=0.053                                           |
|FISHER EXACT           |               P=0.008 **   P=0.045 *    P=0.120    |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  1/70 (1%)    2/61 (3%)    0/63 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   8.0%         0.0%         0.0%         0.0%      |   3.4%         5.1%         0.0%         2.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  2/25 (8%)    0/25 (0%)    0/19 (0%)    0/27 (0%)  |  1/29 (3%)    1/34 (3%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          ---       |   729 (T)      662          ---          698       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.119N     P=0.237N     P=0.300N     P=0.221N   |  P=0.526N     P=0.539      P=0.468N     P=0.751    |
|INCIDENTAL TUMOR       |  P=0.119N     P=0.237N     P=0.300N     P=0.221N   |  P=0.544N     P=0.490      P=0.468N     P=0.726    |
|LOGISTIC REGRESSION    |  P=0.119N     P=0.237N     P=0.300N     P=0.221N   |  P=0.516N     P=0.513      P=0.468N     P=0.751    |
|COCHRAN-ARMITAGE       |  P=0.118N                                          |  P=0.490N                                          |
|FISHER EXACT           |               P=0.288N     P=0.284N     P=0.248N   |               P=0.448      P=0.526N     P=0.752N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   6
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/60 (2%)    1/61 (2%)    0/70 (0%)  |  1/70 (1%)    2/61 (3%)    0/63 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   8.0%         4.0%         2.3%         0.0%      |   3.4%         5.1%         0.0%         2.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  2/25 (8%)    1/25 (4%)    0/19 (0%)    0/27 (0%)  |  1/29 (3%)    1/34 (3%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      617          ---       |   729 (T)      662          ---          698       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.151N     P=0.500N     P=0.550N     P=0.221N   |  P=0.526N     P=0.539      P=0.468N     P=0.751    |
|INCIDENTAL TUMOR       |  P=0.139N     P=0.500N     P=0.469N     P=0.221N   |  P=0.544N     P=0.490      P=0.468N     P=0.726    |
|LOGISTIC REGRESSION    |  P=0.142N     P=0.500N     P=0.481N     P=0.221N   |  P=0.516N     P=0.513      P=0.468N     P=0.751    |
|COCHRAN-ARMITAGE       |  P=0.154N                                          |  P=0.490N                                          |
|FISHER EXACT           |               P=0.558N     P=0.552N     P=0.248N   |               P=0.448      P=0.526N     P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  4/70 (6%)    0/61 (0%)    4/63 (6%)    1/70 (1%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  10.6%         0.0%        10.6%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/25 (0%)    0/19 (0%)    0/27 (0%)  |  1/29 (3%)    0/34 (0%)    2/34 (6%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   451          ---          662          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.285N     P=0.055N     P=0.596N     P=0.194N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.269N     P=0.086N     P=0.594      P=0.163N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.274N     P=0.069N     P=0.636      P=0.187N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.257N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.078N     P=0.581      P=0.183N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   7
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    1/70 (1%)  | 20/70 (29%)  16/61 (26%)  16/63 (25%)  13/70 (19%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         3.7%      |  48.8%        42.8%        42.3%        34.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/25 (0%)    0/19 (0%)    1/27 (4%)  | 10/29 (34%)  13/34 (38%)  13/34 (38%)   7/29 (24%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          729 (T)   |   456 (I)      662          383          466       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.215        (e)          (e)        P=0.515    |  P=0.144N     P=0.164N     P=0.177N     P=0.153N   |
|INCIDENTAL TUMOR       |  P=0.215        (e)          (e)        P=0.515    |  P=0.117N     P=0.292N     P=0.277N     P=0.129N   |
|LOGISTIC REGRESSION    |  P=0.215        (e)          (e)        P=0.515    |  P=0.126N     P=0.230N     P=0.266N     P=0.124N   |
|COCHRAN-ARMITAGE       |  P=0.209                                           |  P=0.094N                                          |
|FISHER EXACT           |                 (e)          (e)        P=0.500    |               P=0.460N     P=0.415N     P=0.116N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    1/70 (1%)  | 23/70 (33%)  16/61 (26%)  19/63 (30%)  14/70 (20%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         3.7%      |  53.9%        42.8%        47.8%        37.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/25 (0%)    0/19 (0%)    1/27 (4%)  | 11/29 (38%)  13/34 (38%)  14/34 (41%)   8/29 (28%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          729 (T)   |   451          662          383          466       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.215        (e)          (e)        P=0.515    |  P=0.114N     P=0.064N     P=0.184N     P=0.091N   |
|INCIDENTAL TUMOR       |  P=0.215        (e)          (e)        P=0.515    |  P=0.081N     P=0.132N     P=0.298N     P=0.059N   |
|LOGISTIC REGRESSION    |  P=0.215        (e)          (e)        P=0.515    |  P=0.092N     P=0.095N     P=0.280N     P=0.065N   |
|COCHRAN-ARMITAGE       |  P=0.209                                           |  P=0.068N                                          |
|FISHER EXACT           |                 (e)          (e)        P=0.500    |               P=0.263N     P=0.442N     P=0.062N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   8
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    0/61 (0%)    1/70 (1%)  | 23/70 (33%)  16/61 (26%)  19/63 (30%)  14/70 (20%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         3.7%      |  53.9%        42.8%        47.8%        37.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/25 (0%)    0/19 (0%)    1/27 (4%)  | 11/29 (38%)  13/34 (38%)  14/34 (41%)   8/29 (28%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          729 (T)   |   451          662          383          466       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.215        (e)          (e)        P=0.515    |  P=0.114N     P=0.064N     P=0.184N     P=0.091N   |
|INCIDENTAL TUMOR       |  P=0.215        (e)          (e)        P=0.515    |  P=0.081N     P=0.132N     P=0.298N     P=0.059N   |
|LOGISTIC REGRESSION    |  P=0.215        (e)          (e)        P=0.515    |  P=0.092N     P=0.095N     P=0.280N     P=0.065N   |
|COCHRAN-ARMITAGE       |  P=0.209                                           |  P=0.068N                                          |
|FISHER EXACT           |                 (e)          (e)        P=0.500    |               P=0.263N     P=0.442N     P=0.062N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/70 (11%)   7/60 (12%)   7/60 (12%)   9/69 (13%) | 22/70 (31%)  21/61 (34%)  25/63 (40%)  28/70 (40%) |
|ADJUSTED (b)           |  26.6%        21.7%        22.1%        28.9%      |  56.3%        51.5%        60.4%        73.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  1/10 (10%)   1/10 (10%)   0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  5/25 (20%)   3/25 (12%)   2/19 (11%)   6/26 (23%) | 13/29 (45%)  15/34 (44%)  18/34 (53%)  19/29 (66%) |
|FIRST INCIDENCE (DAYS) |   539          456 (I)      626          522       |   451          456 (I)      635          466       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.448      P=0.488N     P=0.562N     P=0.551    |  P=0.073      P=0.311N     P=0.558      P=0.171    |
|INCIDENTAL TUMOR       |  P=0.447      P=0.494N     P=0.414N     P=0.521    |  P=0.058      P=0.498N     P=0.339      P=0.120    |
|LOGISTIC REGRESSION    |  P=0.439      P=0.456N     P=0.469N     P=0.546    |  P=0.056      P=0.465N     P=0.362      P=0.115    |
|COCHRAN-ARMITAGE       |  P=0.429                                           |  P=0.152                                           |
|FISHER EXACT           |               P=0.590      P=0.590      P=0.487    |               P=0.429      P=0.208      P=0.189    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE   9
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/70 (11%)   7/60 (12%)   7/60 (12%)   9/69 (13%) | 22/70 (31%)  22/61 (36%)  25/63 (40%)  28/70 (40%) |
|ADJUSTED (b)           |  26.6%        21.7%        22.1%        28.9%      |  56.3%        54.1%        60.4%        73.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  1/10 (10%)   1/10 (10%)   0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  5/25 (20%)   3/25 (12%)   2/19 (11%)   6/26 (23%) | 13/29 (45%)  16/34 (47%)  18/34 (53%)  19/29 (66%) |
|FIRST INCIDENCE (DAYS) |   539          456 (I)      626          522       |   451          456 (I)      635          466       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.448      P=0.488N     P=0.562N     P=0.551    |  P=0.082      P=0.372N     P=0.558      P=0.171    |
|INCIDENTAL TUMOR       |  P=0.447      P=0.494N     P=0.414N     P=0.521    |  P=0.066      P=0.571N     P=0.339      P=0.120    |
|LOGISTIC REGRESSION    |  P=0.439      P=0.456N     P=0.469N     P=0.546    |  P=0.064      P=0.542N     P=0.362      P=0.115    |
|COCHRAN-ARMITAGE       |  P=0.429                                           |  P=0.168                                           |
|FISHER EXACT           |               P=0.590      P=0.590      P=0.487    |               P=0.353      P=0.208      P=0.189    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basosquamous Tumor Malignant                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   6.6%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/25 (0%)    0/19 (0%)    0/27 (0%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   645          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.114N     P=0.234N     P=0.261N     P=0.223N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.105N     P=0.223N     P=0.205N     P=0.223N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.109N     P=0.226N     P=0.226N     P=0.222N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.118N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.288N     P=0.284N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  10
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    2/60 (3%)    1/61 (2%)    1/70 (1%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   6.6%         8.0%         2.3%         3.7%      |   0.0%         0.0%         0.0%         2.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    2/25 (8%)    0/19 (0%)    1/27 (4%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   645          729 (T)      617          729 (T)   |   ---          ---          ---          698       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.323N     P=0.690N     P=0.509N     P=0.473N   |  P=0.183        (e)          (e)        P=0.484    |
|INCIDENTAL TUMOR       |  P=0.309N     P=0.681N     P=0.373N     P=0.473N   |  P=0.181        (e)          (e)        P=0.438    |
|LOGISTIC REGRESSION    |  P=0.317N     P=0.677N     P=0.487N     P=0.474N   |  P=0.192        (e)          (e)        P=0.492    |
|COCHRAN-ARMITAGE       |  P=0.330N                                          |  P=0.208                                           |
|FISHER EXACT           |               P=0.630      P=0.552N     P=0.500N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/60 (3%)    1/61 (2%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         8.0%         5.3%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    2/25 (8%)    1/19 (5%)    0/27 (0%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      729 (T)      ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.448N     P=0.237      P=0.445        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.448N     P=0.237      P=0.445        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.448N     P=0.237      P=0.445        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.453N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.211      P=0.466        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  11
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    5/60 (8%)    3/61 (5%)    1/70 (1%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |  10.5%        18.2%        10.4%         3.7%      |   0.0%         0.0%         0.0%         2.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  2/25 (8%)    4/25 (16%)   1/19 (5%)    1/27 (4%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   645          652          617          729 (T)   |   ---          ---          ---          698       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.147N     P=0.366      P=0.613      P=0.279N   |  P=0.183        (e)          (e)        P=0.484    |
|INCIDENTAL TUMOR       |  P=0.134N     P=0.377      P=0.579N     P=0.279N   |  P=0.181        (e)          (e)        P=0.438    |
|LOGISTIC REGRESSION    |  P=0.138N     P=0.384      P=0.637N     P=0.279N   |  P=0.192        (e)          (e)        P=0.492    |
|COCHRAN-ARMITAGE       |  P=0.155N                                          |  P=0.208                                           |
|FISHER EXACT           |               P=0.277      P=0.592      P=0.310N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    2/60 (3%)    3/61 (5%)    2/70 (3%)  |  0/70 (0%)    2/61 (3%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   3.3%         6.2%        12.4%         4.7%      |   0.0%         5.1%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/25 (4%)    1/19 (5%)    0/27 (0%)  |  0/29 (0%)    1/34 (3%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   709          611          691          558       |   ---          611          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.423      P=0.510      P=0.245      P=0.523    |  P=0.408N     P=0.262        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.448      P=0.612      P=0.433      P=0.577    |  P=0.388N     P=0.257        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.428      P=0.518      P=0.308      P=0.518    |  P=0.409N     P=0.232        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.422                                           |  P=0.401N                                          |
|FISHER EXACT           |               P=0.442      P=0.260      P=0.500    |               P=0.215        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  12
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    2/60 (3%)    3/61 (5%)    2/70 (3%)  |  1/70 (1%)    2/61 (3%)    0/63 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   3.3%         6.2%        12.4%         4.7%      |   3.4%         5.1%         0.0%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/25 (4%)    1/19 (5%)    0/27 (0%)  |  1/29 (3%)    1/34 (3%)    0/34 (0%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   709          611          691          558       |   729 (T)      611          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.423      P=0.510      P=0.245      P=0.523    |  P=0.509N     P=0.542      P=0.468N     P=0.762    |
|INCIDENTAL TUMOR       |  P=0.448      P=0.612      P=0.433      P=0.577    |  P=0.491N     P=0.537      P=0.468N     P=0.762    |
|LOGISTIC REGRESSION    |  P=0.428      P=0.518      P=0.308      P=0.518    |  P=0.514N     P=0.504      P=0.468N     P=0.762    |
|COCHRAN-ARMITAGE       |  P=0.422                                           |  P=0.490N                                          |
|FISHER EXACT           |               P=0.442      P=0.260      P=0.500    |               P=0.448      P=0.526N     P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Leiomyosarcoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/60 (0%)    0/61 (0%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   8.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  2/25 (8%)    0/25 (0%)    0/19 (0%)    0/27 (0%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.119N     P=0.237N     P=0.300N     P=0.221N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.119N     P=0.237N     P=0.300N     P=0.221N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.119N     P=0.237N     P=0.300N     P=0.221N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.118N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.288N     P=0.284N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  13
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 52/70 (74%)  48/60 (80%)  55/61 (90%)  57/69 (83%) |                                                    |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)| 10/10 (100%)  1/10 (10%)   6/10 (60%)  10/10 (100%)|                                                    |
|TERMINAL (d)           | 25/25 (100%) 25/25 (100%) 19/19 (100%) 27/27 (100%)|                                                    |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      456 (I)      456 (I)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.289      P=0.279N     P=0.127      P=0.453    |                                                    |
|INCIDENTAL TUMOR       |  P=0.080      P=0.004N**   P=0.356N     P=0.396    |                                                    |
|LOGISTIC REGRESSION    |  P=0.053      P=0.012N*    P=0.466N     P=0.248    |                                                    |
|COCHRAN-ARMITAGE       |  P=0.112                                           |                                                    |
|FISHER EXACT           |               P=0.288      P=0.016 *    P=0.162    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/70 (16%)   7/59 (12%)  12/61 (20%)  10/69 (14%) |  5/70 (7%)   11/61 (18%)   6/63 (10%)  10/70 (14%) |
|ADJUSTED (b)           |  33.3%        21.7%        41.5%        29.1%      |  17.2%        30.1%        17.1%        29.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  6/25 (24%)   4/25 (16%)   5/19 (26%)   6/27 (22%) |  5/29 (17%)   9/34 (26%)   5/34 (15%)   7/29 (24%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      610          552          456 (I)   |   729 (T)      666          723          634       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.534N     P=0.210N     P=0.367      P=0.428N   |  P=0.178      P=0.146      P=0.611      P=0.122    |
|INCIDENTAL TUMOR       |  P=0.536N     P=0.172N     P=0.551      P=0.498N   |  P=0.170      P=0.116      P=0.577      P=0.118    |
|LOGISTIC REGRESSION    |  P=0.532N     P=0.210N     P=0.559      P=0.444N   |  P=0.163      P=0.113      P=0.593      P=0.107    |
|COCHRAN-ARMITAGE       |  P=0.526                                           |  P=0.251                                           |
|FISHER EXACT           |               P=0.357N     P=0.357      P=0.514N   |               P=0.051      P=0.426      P=0.137    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  14
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/70 (16%)   7/59 (12%)  12/61 (20%)  10/69 (14%) |  5/70 (7%)   11/61 (18%)   7/63 (11%)  10/70 (14%) |
|ADJUSTED (b)           |  33.3%        21.7%        41.5%        29.1%      |  17.2%        30.1%        20.0%        29.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  6/25 (24%)   4/25 (16%)   5/19 (26%)   6/27 (22%) |  5/29 (17%)   9/34 (26%)   6/34 (18%)   7/29 (24%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      610          552          456 (I)   |   729 (T)      666          723          634       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.534N     P=0.210N     P=0.367      P=0.428N   |  P=0.171      P=0.146      P=0.494      P=0.122    |
|INCIDENTAL TUMOR       |  P=0.536N     P=0.172N     P=0.551      P=0.498N   |  P=0.164      P=0.116      P=0.459      P=0.118    |
|LOGISTIC REGRESSION    |  P=0.532N     P=0.210N     P=0.559      P=0.444N   |  P=0.156      P=0.113      P=0.472      P=0.107    |
|COCHRAN-ARMITAGE       |  P=0.526                                           |  P=0.245                                           |
|FISHER EXACT           |               P=0.357N     P=0.357      P=0.514N   |               P=0.051      P=0.310      P=0.137    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/59 (2%)    2/61 (3%)    2/69 (3%)  |  0/70 (0%)    0/61 (0%)    1/63 (2%)    1/70 (1%)  |
|ADJUSTED (b)           |   4.0%         2.6%         9.4%         6.7%      |   0.0%         0.0%         2.9%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/25 (0%)    1/19 (5%)    1/27 (4%)  |  0/29 (0%)    0/34 (0%)    1/34 (3%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      652          713          702       |   ---          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.355      P=0.751N     P=0.410      P=0.522    |  P=0.222        (e)        P=0.532      P=0.500    |
|INCIDENTAL TUMOR       |  P=0.365      P=0.751N     P=0.500      P=0.527    |  P=0.222        (e)        P=0.532      P=0.500    |
|LOGISTIC REGRESSION    |  P=0.360      P=0.755N     P=0.458      P=0.521    |  P=0.222        (e)        P=0.532      P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.351                                           |  P=0.247                                           |
|FISHER EXACT           |               P=0.707      P=0.448      P=0.495    |                 (e)        P=0.474      P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  15
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/59 (2%)    2/61 (3%)    2/69 (3%)  |  0/70 (0%)    0/61 (0%)    2/63 (3%)    1/70 (1%)  |
|ADJUSTED (b)           |   4.0%         2.6%         9.4%         6.7%      |   0.0%         0.0%         5.9%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/25 (4%)    0/25 (0%)    1/19 (5%)    1/27 (4%)  |  0/29 (0%)    0/34 (0%)    2/34 (6%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      652          713          702       |   ---          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.355      P=0.751N     P=0.410      P=0.522    |  P=0.230        (e)        P=0.274      P=0.500    |
|INCIDENTAL TUMOR       |  P=0.365      P=0.751N     P=0.500      P=0.527    |  P=0.230        (e)        P=0.274      P=0.500    |
|LOGISTIC REGRESSION    |  P=0.360      P=0.755N     P=0.458      P=0.521    |  P=0.230        (e)        P=0.274      P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.351                                           |  P=0.258                                           |
|FISHER EXACT           |               P=0.707      P=0.448      P=0.495    |                 (e)        P=0.222      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Leiomyoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/70 (0%)    0/61 (0%)    0/63 (0%)    2/70 (3%)  |
|ADJUSTED (b)           |                                                    |   0.0%         0.0%         0.0%         5.6%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |                                                    |  0/29 (0%)    0/34 (0%)    0/34 (0%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          ---          ---          619       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.043 *      (e)          (e)        P=0.240    |
|INCIDENTAL TUMOR       |                                                    |  P=0.055        (e)          (e)        P=0.264    |
|LOGISTIC REGRESSION    |                                                    |  P=0.045 *      (e)          (e)        P=0.232    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.053                                           |
|FISHER EXACT           |                                                    |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  16
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  5/70 (7%)    7/61 (11%)   5/63 (8%)    5/70 (7%)  |
|ADJUSTED (b)           |                                                    |  12.9%        18.4%        14.3%        16.1%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  1/10 (10%)   1/10 (10%)   0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |                                                    |  2/29 (7%)    5/34 (15%)   4/34 (12%)   4/29 (14%) |
|FIRST INCIDENCE (DAYS) |                                                    |   456 (I)      456 (I)      723          685       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.499N     P=0.463      P=0.556N     P=0.617    |
|INCIDENTAL TUMOR       |                                                    |  P=0.515N     P=0.400      P=0.620      P=0.604    |
|LOGISTIC REGRESSION    |                                                    |  P=0.498N     P=0.362      P=0.625      P=0.613    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.446N                                          |
|FISHER EXACT           |                                                    |               P=0.289      P=0.560      P=0.628N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/60 (0%)    2/61 (3%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         8.1%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/25 (0%)    1/19 (5%)    0/27 (0%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          688          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.605        (e)        P=0.216        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.611        (e)        P=0.266        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.607        (e)        P=0.242        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.599                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.215        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  17
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    1/60 (2%)    2/61 (3%)    0/70 (0%)  |  0/70 (0%)    0/61 (0%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         2.3%         8.1%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    0/25 (0%)    1/19 (5%)    0/27 (0%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          611          688          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.600N     P=0.524      P=0.216        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.590N     P=0.669      P=0.266        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.602N     P=0.483      P=0.242        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.604N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.462      P=0.215        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 22/70 (31%)  23/60 (38%)  19/61 (31%)  18/70 (26%) |  8/70 (11%)  11/61 (18%)   7/63 (11%)   9/70 (13%) |
|ADJUSTED (b)           |  57.6%        55.9%        50.0%        49.1%      |  19.8%        23.8%        16.2%        24.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           | 10/25 (40%)   9/25 (36%)   4/19 (21%)  11/27 (41%) |  1/29 (3%)    2/34 (6%)    1/34 (3%)    3/29 (10%) |
|FIRST INCIDENCE (DAYS) |   508          539          541          368       |   534          522          619          589       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.163N     P=0.552      P=0.463N     P=0.209N   |  P=0.499      P=0.392      P=0.454N     P=0.471    |
|INCIDENTAL TUMOR       |  P=0.095N     P=0.421N     P=0.079N     P=0.140N   |  P=0.525      P=0.131      P=0.509      P=0.401    |
|LOGISTIC REGRESSION    |  P=0.091N     P=0.294N     P=0.043N*    P=0.194N   |  P=0.428N     P=0.168      P=0.576N     P=0.538    |
|COCHRAN-ARMITAGE       |  P=0.165N                                          |  P=0.504N                                          |
|FISHER EXACT           |               P=0.261      P=0.562N     P=0.287N   |               P=0.205      P=0.587N     P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  18
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/60 (3%)    0/61 (0%)    1/70 (1%)  |  1/70 (1%)    0/61 (0%)    0/63 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         6.0%         0.0%         3.7%      |   3.3%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/25 (0%)    1/25 (4%)    0/19 (0%)    1/27 (4%)  |  0/29 (0%)    0/34 (0%)    0/34 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          542          ---          729 (T)   |   725          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.556      P=0.257        (e)        P=0.515    |  P=0.308N     P=0.475N     P=0.475N     P=0.507N   |
|INCIDENTAL TUMOR       |  P=0.539      P=0.166        (e)        P=0.515    |  P=0.345N     P=0.581N     P=0.581N     P=0.562N   |
|LOGISTIC REGRESSION    |  P=0.553      P=0.229        (e)        P=0.515    |  P=0.311N     P=0.481N     P=0.486N     P=0.511N   |
|COCHRAN-ARMITAGE       |  P=0.547                                           |  P=0.306N                                          |
|FISHER EXACT           |               P=0.211        (e)        P=0.500    |               P=0.534N     P=0.526N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 54/70 (77%)  50/60 (83%)  58/61 (95%)  58/70 (83%) | 43/70 (61%)  39/61 (64%)  40/63 (63%)  37/70 (53%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  89.2%        86.2%        88.7%        83.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)| 10/10 (100%)  2/10 (20%)   8/10 (80%)  10/10 (100%)|  3/10 (30%)   2/10 (20%)   0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           | 25/25 (100%) 25/25 (100%) 19/19 (100%) 27/27 (100%)| 24/29 (83%)  28/34 (82%)  29/34 (85%)  22/29 (76%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      456 (I)      456 (I)   |   451          456 (I)      383          466       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.344      P=0.280N     P=0.108      P=0.529    |  P=0.313N     P=0.099N     P=0.139N     P=0.266N   |
|INCIDENTAL TUMOR       |  P=0.215      P=0.004N**   P=0.571N     P=0.662N   |  P=0.187N     P=0.233N     P=0.332N     P=0.192N   |
|LOGISTIC REGRESSION    |  P=0.151      P=0.007N**   P=0.689N     P=0.562    |  P=0.219N     P=0.223N     P=0.335N     P=0.188N   |
|COCHRAN-ARMITAGE       |  P=0.199                                           |  P=0.136N                                          |
|FISHER EXACT           |               P=0.256      P=0.003 **   P=0.263    |               P=0.455      P=0.474      P=0.197N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  19
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        150 PPM      300 PPM      600 PPM   |   0 PPM        150 PPM      300 PPM      600 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 26/70 (37%)  30/60 (50%)  24/61 (39%)  23/70 (33%) | 16/70 (23%)  13/61 (21%)   9/63 (14%)  10/70 (14%) |
|ADJUSTED (b)           |  67.0%        67.4%        59.0%        58.9%      |  36.5%        28.6%        21.3%        25.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |
|TERMINAL (d)           | 13/25 (52%)  12/25 (48%)   5/19 (26%)  13/27 (48%) |  3/29 (10%)   4/34 (12%)   3/34 (9%)    3/29 (10%) |
|FIRST INCIDENCE (DAYS) |   508          366          541          368       |   534          522          619          456 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.176N     P=0.375      P=0.560N     P=0.257N   |  P=0.146N     P=0.264N     P=0.081N     P=0.183N   |
|INCIDENTAL TUMOR       |  P=0.092N     P=0.487      P=0.081N     P=0.171N   |  P=0.090N     P=0.525N     P=0.187N     P=0.162N   |
|LOGISTIC REGRESSION    |  P=0.094N     P=0.542      P=0.038N*    P=0.187N   |  P=0.045N*    P=0.500N     P=0.143N     P=0.092N   |
|COCHRAN-ARMITAGE       |  P=0.173N                                          |  P=0.087N                                          |
|FISHER EXACT           |               P=0.097      P=0.468      P=0.362N   |               P=0.500N     P=0.149N     P=0.139N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 55/70 (79%)  52/60 (87%)  58/61 (95%)  60/70 (86%) | 49/70 (70%)  45/61 (74%)  42/63 (67%)  42/70 (60%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  94.1%        88.1%        89.3%        87.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/1 (0%)     0/10 (0%)  |  0/10 (0%)    0/1 (0%)     0/3 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)| 10/10 (100%)  3/10 (30%)   8/10 (80%)  10/10 (100%)|  3/10 (30%)   2/10 (20%)   0/10 (0%)    1/10 (10%) |
|TERMINAL (d)           | 25/25 (100%) 25/25 (100%) 19/19 (100%) 27/27 (100%)| 26/29 (90%)  28/34 (82%)  29/34 (85%)  23/29 (79%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      366          456 (I)      368       |   451          456 (I)      383          456 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.320      P=0.329N     P=0.141      P=0.474    |  P=0.260N     P=0.106N     P=0.047N*    P=0.237N   |
|INCIDENTAL TUMOR       |  P=0.101      P=0.013N*    P=0.421N     P=0.536    |  P=0.061N     P=0.233N     P=0.068N     P=0.075N   |
|LOGISTIC REGRESSION    |  P=0.064      P=0.019N*    P=0.465N     P=0.275    |  P=0.063N     P=0.228N     P=0.074N     P=0.066N   |
|COCHRAN-ARMITAGE       |  P=0.152                                           |  P=0.072N                                          |
|FISHER EXACT           |               P=0.165      P=0.005 **   P=0.189    |               P=0.389      P=0.410N     P=0.144N   |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 01                                                 PAGE  20
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIAMTERENE
 
                                                 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):   93  456
          Female interim sacrifices(days): 93  456
 (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).
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.