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TDMS Study 05087-03 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                        TRIAMTERENE                                      DATE: 09/11/94       
EXPERIMENT: 05087 TEST: 03                                                                                     TIME: 15:33:27       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 56042B       
PATHOLOGIST: L. MEZZA                        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: 03                                                                                     TIME: 15:33:27      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 56042B      
PATHOLOGIST: L. MEZZA                        S. EUSTIS                                                         CAS: 396-01-0       
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                        TRIAMTERENE                                      DATE: 09/11/94       
EXPERIMENT: 05087 TEST: 03                                                                                     TIME: 15:33:27       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-45041          ROUTE: DOSED FEED                                                                  NTP C#: 56042B       
PATHOLOGIST: L. MEZZA                        S. EUSTIS                                                         CAS: 396-01-0        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                          IN THE ANALYSIS OF THE STUDY OF TRIAMTERENE
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Harderian Gland               Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             All Organs                    Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             All Organs                    Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   1
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         0/60 (0%)           1/60 (2%)              |         2/60 (3%)           2/60 (3%)              |
|ADJUSTED (b)           |          0.0%                2.6%                  |          5.0%                5.3%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         0/43 (0%)           1/39 (3%)              |         2/40 (5%)           2/38 (5%)              |
|FIRST INCIDENCE (DAYS) |          ---                 729 (T)               |          730 (T)             730 (T)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.481                |                             P=0.676                |
|INCIDENTAL TUMOR       |                             P=0.481                |                             P=0.676                |
|LOGISTIC REGRESSION    |                             P=0.481                |                             P=0.676                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.500                |                             P=0.691N               |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         1/60 (2%)           0/60 (0%)              |         2/60 (3%)           0/60 (0%)              |
|ADJUSTED (b)           |          2.3%                0.0%                  |          5.0%                0.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         1/43 (2%)           0/39 (0%)              |         2/40 (5%)           0/38 (0%)              |
|FIRST INCIDENCE (DAYS) |          729 (T)             ---                   |          730 (T)             ---                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.519N               |                             P=0.250N               |
|INCIDENTAL TUMOR       |                             P=0.519N               |                             P=0.250N               |
|LOGISTIC REGRESSION    |                             P=0.519N               |                             P=0.250N               |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.500N               |                             P=0.248N               |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   2
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         1/60 (2%)           6/60 (10%)             |         0/60 (0%)           3/60 (5%)              |
|ADJUSTED (b)           |          2.3%               15.4%                  |          0.0%                7.4%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         1/43 (2%)           6/39 (15%)             |         0/40 (0%)           1/38 (3%)              |
|FIRST INCIDENCE (DAYS) |          729 (T)             729 (T)               |          ---                 687                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.044 *              |                             P=0.113                |
|INCIDENTAL TUMOR       |                             P=0.044 *              |                             P=0.182                |
|LOGISTIC REGRESSION    |                             P=0.044 *              |                             P=0.119                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.057                |                             P=0.122                |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         2/57 (4%)           0/59 (0%)              |         1/59 (2%)           0/57 (0%)              |
|ADJUSTED (b)           |          4.0%                0.0%                  |          2.5%                0.0%                  |
|INTERIM SACRIFICE 1 (c)|         1/10 (10%)          0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         1/42 (2%)           0/39 (0%)              |         1/40 (3%)           0/38 (0%)              |
|FIRST INCIDENCE (DAYS) |          463 (I)             ---                   |          730 (T)             ---                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.248N               |                             P=0.510N               |
|INCIDENTAL TUMOR       |                             P=0.248N               |                             P=0.510N               |
|LOGISTIC REGRESSION    |                             P=0.227N               |                             P=0.510N               |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.239N               |                             P=0.509N               |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   3
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         2/60 (3%)           1/60 (2%)              |         0/60 (0%)           0/60 (0%)              |
|ADJUSTED (b)           |          4.7%                2.6%                  |          0.0%                0.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         2/43 (5%)           1/39 (3%)              |         0/40 (0%)           0/38 (0%)              |
|FIRST INCIDENCE (DAYS) |          729 (T)             729 (T)               |          ---                 ---                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.534N               |           (e)                 (e)                  |
|INCIDENTAL TUMOR       |                             P=0.534N               |           (e)                 (e)                  |
|LOGISTIC REGRESSION    |                             P=0.534N               |           (e)                 (e)                  |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.500N               |                               (e)                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |        21/60 (35%)         37/60 (62%)             |         7/60 (12%)         28/60 (47%)             |
|ADJUSTED (b)           |         44.7%               82.0%                  |         17.5%               70.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           1/10 (10%)             |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |        17/43 (40%)         31/39 (79%)             |         7/40 (18%)         26/38 (68%)             |
|FIRST INCIDENCE (DAYS) |          701                 463 (I)               |          730 (T)             687                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P<0.001 **             |                             P<0.001 **             |
|INCIDENTAL TUMOR       |                             P=0.001 **             |                             P<0.001 **             |
|LOGISTIC REGRESSION    |                             P<0.001 **             |                             P<0.001 **             |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.003 **             |                             P<0.001 **             |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   4
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         9/60 (15%)         11/60 (18%)             |         6/60 (10%)         11/60 (18%)             |
|ADJUSTED (b)           |         19.3%               25.0%                  |         13.4%               28.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         1/10 (10%)          0/9 (0%)               |
|TERMINAL (d)           |         6/43 (14%)          7/39 (18%)             |         4/40 (10%)         10/38 (26%)             |
|FIRST INCIDENCE (DAYS) |          622                 494                   |          463 (I)             676                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.329                |                             P=0.124                |
|INCIDENTAL TUMOR       |                             P=0.486                |                             P=0.139                |
|LOGISTIC REGRESSION    |                             P=0.519                |                             P=0.141                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.404                |                             P=0.148                |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         9/60 (15%)         12/60 (20%)             |         6/60 (10%)         11/60 (18%)             |
|ADJUSTED (b)           |         19.3%               26.7%                  |         13.4%               28.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         1/10 (10%)          0/9 (0%)               |
|TERMINAL (d)           |         6/43 (14%)          7/39 (18%)             |         4/40 (10%)         10/38 (26%)             |
|FIRST INCIDENCE (DAYS) |          622                 494                   |          463 (I)             676                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.254                |                             P=0.124                |
|INCIDENTAL TUMOR       |                             P=0.436                |                             P=0.139                |
|LOGISTIC REGRESSION    |                             P=0.468                |                             P=0.141                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.316                |                             P=0.148                |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   5
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |        25/60 (42%)         39/60 (65%)             |        11/60 (18%)         31/60 (52%)             |
|ADJUSTED (b)           |         52.1%               82.8%                  |         25.4%               75.6%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           1/10 (10%)             |         1/10 (10%)          0/9 (0%)               |
|TERMINAL (d)           |        20/43 (47%)         31/39 (79%)             |         9/40 (23%)         28/38 (74%)             |
|FIRST INCIDENCE (DAYS) |          622                 463 (I)               |          463 (I)             676                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.003 **             |                             P<0.001 **             |
|INCIDENTAL TUMOR       |                             P=0.005 **             |                             P<0.001 **             |
|LOGISTIC REGRESSION    |                             P=0.002 **             |                             P<0.001 **             |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.009 **             |                             P<0.001 **             |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |        25/60 (42%)         39/60 (65%)             |        11/60 (18%)         31/60 (52%)             |
|ADJUSTED (b)           |         52.1%               82.8%                  |         25.4%               75.6%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           1/10 (10%)             |         1/10 (10%)          0/9 (0%)               |
|TERMINAL (d)           |        20/43 (47%)         31/39 (79%)             |         9/40 (23%)         28/38 (74%)             |
|FIRST INCIDENCE (DAYS) |          622                 463 (I)               |          463 (I)             676                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.003 **             |                             P<0.001 **             |
|INCIDENTAL TUMOR       |                             P=0.005 **             |                             P<0.001 **             |
|LOGISTIC REGRESSION    |                             P=0.002 **             |                             P<0.001 **             |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.009 **             |                             P<0.001 **             |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   6
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         6/60 (10%)         10/60 (17%)             |         2/60 (3%)           0/60 (0%)              |
|ADJUSTED (b)           |         14.0%               24.6%                  |          5.0%                0.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         6/43 (14%)          9/39 (23%)             |         2/40 (5%)           0/38 (0%)              |
|FIRST INCIDENCE (DAYS) |          729 (T)             494                   |          730 (T)             ---                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.154                |                             P=0.250N               |
|INCIDENTAL TUMOR       |                             P=0.154                |                             P=0.250N               |
|LOGISTIC REGRESSION    |                             P=0.183                |                             P=0.250N               |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.211                |                             P=0.248N               |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         7/60 (12%)          6/60 (10%)             |         1/60 (2%)           1/60 (2%)              |
|ADJUSTED (b)           |         15.7%               15.4%                  |          2.5%                2.6%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         6/43 (14%)          6/39 (15%)             |         1/40 (3%)           1/38 (3%)              |
|FIRST INCIDENCE (DAYS) |          534                 729 (T)               |          730 (T)             730 (T)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.570N               |                             P=0.750                |
|INCIDENTAL TUMOR       |                             P=0.569N               |                             P=0.750                |
|LOGISTIC REGRESSION    |                             P=0.530N               |                             P=0.750                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.500N               |                             P=0.752N               |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   7
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |        13/60 (22%)         16/60 (27%)             |         3/60 (5%)           1/60 (2%)              |
|ADJUSTED (b)           |         29.4%               39.7%                  |          7.5%                2.6%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |        12/43 (28%)         15/39 (38%)             |         3/40 (8%)           1/38 (3%)              |
|FIRST INCIDENCE (DAYS) |          534                 494                   |          730 (T)             730 (T)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.231                |                             P=0.324N               |
|INCIDENTAL TUMOR       |                             P=0.227                |                             P=0.324N               |
|LOGISTIC REGRESSION    |                             P=0.287                |                             P=0.324N               |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.335                |                             P=0.309N               |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         0/60 (0%)           1/58 (2%)              |         1/59 (2%)           3/56 (5%)              |
|ADJUSTED (b)           |          0.0%                2.6%                  |          2.6%                8.6%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         0/43 (0%)           1/39 (3%)              |         1/39 (3%)           3/35 (9%)              |
|FIRST INCIDENCE (DAYS) |          ---                 729 (T)               |          730 (T)             730 (T)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.481                |                             P=0.267                |
|INCIDENTAL TUMOR       |                             P=0.481                |                             P=0.267                |
|LOGISTIC REGRESSION    |                             P=0.481                |                             P=0.267                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.492                |                             P=0.290                |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   8
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         0/60 (0%)           1/58 (2%)              |         1/59 (2%)           4/56 (7%)              |
|ADJUSTED (b)           |          0.0%                2.6%                  |          2.6%               11.4%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         0/43 (0%)           1/39 (3%)              |         1/39 (3%)           4/35 (11%)             |
|FIRST INCIDENCE (DAYS) |          ---                 729 (T)               |          730 (T)             730 (T)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.481                |                             P=0.148                |
|INCIDENTAL TUMOR       |                             P=0.481                |                             P=0.148                |
|LOGISTIC REGRESSION    |                             P=0.481                |                             P=0.148                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.492                |                             P=0.166                |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         2/57 (4%)           0/60 (0%)              |         3/59 (5%)           0/60 (0%)              |
|ADJUSTED (b)           |          4.8%                0.0%                  |          7.0%                0.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         2/42 (5%)           0/39 (0%)              |         2/40 (5%)           0/38 (0%)              |
|FIRST INCIDENCE (DAYS) |          729 (T)             ---                   |          555                 ---                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.255N               |                             P=0.128N               |
|INCIDENTAL TUMOR       |                             P=0.255N               |                             P=0.105N               |
|LOGISTIC REGRESSION    |                             P=0.255N               |                             P=0.118N               |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.235N               |                             P=0.119N               |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE   9
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         4/60 (7%)           1/60 (2%)              |         3/60 (5%)           0/60 (0%)              |
|ADJUSTED (b)           |          9.3%                2.6%                  |          7.0%                0.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         4/43 (9%)           1/39 (3%)              |         2/40 (5%)           0/38 (0%)              |
|FIRST INCIDENCE (DAYS) |          729 (T)             729 (T)               |          555                 ---                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.210N               |                             P=0.128N               |
|INCIDENTAL TUMOR       |                             P=0.210N               |                             P=0.129N               |
|LOGISTIC REGRESSION    |                             P=0.210N               |                             P=0.121N               |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.182N               |                             P=0.122N               |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         4/60 (7%)           2/60 (3%)              |         3/60 (5%)           0/60 (0%)              |
|ADJUSTED (b)           |          9.3%                5.1%                  |          7.0%                0.0%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |         4/43 (9%)           2/39 (5%)              |         2/40 (5%)           0/38 (0%)              |
|FIRST INCIDENCE (DAYS) |          729 (T)             729 (T)               |          555                 ---                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.383N               |                             P=0.128N               |
|INCIDENTAL TUMOR       |                             P=0.383N               |                             P=0.129N               |
|LOGISTIC REGRESSION    |                             P=0.383N               |                             P=0.121N               |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.340N               |                             P=0.122N               |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE  10
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         5/60 (8%)           9/60 (15%)             |         9/60 (15%)         17/60 (28%)             |
|ADJUSTED (b)           |         10.4%               19.4%                  |         19.9%               34.9%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           2/9 (22%)              |
|TERMINAL (d)           |         2/43 (5%)           3/39 (8%)              |         5/40 (13%)          8/38 (21%)             |
|FIRST INCIDENCE (DAYS) |          440                 522                   |          534                 463 (I)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.177                |                             P=0.062                |
|INCIDENTAL TUMOR       |                             P=0.345                |                             P=0.092                |
|LOGISTIC REGRESSION    |                             P=0.328                |                             P=0.094                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.197                |                             P=0.060                |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |         5/60 (8%)           9/60 (15%)             |         9/60 (15%)         17/60 (28%)             |
|ADJUSTED (b)           |         10.4%               19.4%                  |         19.9%               34.9%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         0/10 (0%)           2/9 (22%)              |
|TERMINAL (d)           |         2/43 (5%)           3/39 (8%)              |         5/40 (13%)          8/38 (21%)             |
|FIRST INCIDENCE (DAYS) |          440                 522                   |          534                 463 (I)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.177                |                             P=0.062                |
|INCIDENTAL TUMOR       |                             P=0.345                |                             P=0.092                |
|LOGISTIC REGRESSION    |                             P=0.328                |                             P=0.094                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.197                |                             P=0.060                |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE  11
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |        26/60 (43%)         40/60 (67%)             |        12/60 (20%)         31/60 (52%)             |
|ADJUSTED (b)           |         54.0%               86.8%                  |         30.0%               75.6%                  |
|INTERIM SACRIFICE 1 (c)|         1/10 (10%)          1/10 (10%)             |         0/10 (0%)           0/9 (0%)               |
|TERMINAL (d)           |        21/43 (49%)         33/39 (85%)             |        12/40 (30%)         28/38 (74%)             |
|FIRST INCIDENCE (DAYS) |          463 (I)             463 (I)               |          730 (T)             687                   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.002 **             |                             P<0.001 **             |
|INCIDENTAL TUMOR       |                             P=0.003 **             |                             P<0.001 **             |
|LOGISTIC REGRESSION    |                             P=0.002 **             |                             P<0.001 **             |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.008 **             |                             P<0.001 **             |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |        25/60 (42%)         26/60 (43%)             |        24/60 (40%)         30/60 (50%)             |
|ADJUSTED (b)           |         49.8%               52.0%                  |         48.7%               60.6%                  |
|INTERIM SACRIFICE 1 (c)|         0/10 (0%)           0/10 (0%)              |         1/10 (10%)          2/9 (22%)              |
|TERMINAL (d)           |        18/43 (42%)         15/39 (38%)             |        15/40 (38%)         19/38 (50%)             |
|FIRST INCIDENCE (DAYS) |          440                 494                   |          463 (I)             463 (I)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.369                |                             P=0.161                |
|INCIDENTAL TUMOR       |                             P=0.465N               |                             P=0.244                |
|LOGISTIC REGRESSION    |                             P=0.426N               |                             P=0.247                |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.500                |                             P=0.179                |
|=================================================================================================================================|
 
         DATE: 09/11/94                     EXPERIMENT: 05087 TEST: 03                                                 PAGE  12
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TRIAMTERENE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |          0PPM                400 PPM               |          0PPM                400 PPM               |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |           #                   #                    |           #                   #                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |        38/60 (63%)         45/60 (75%)             |        30/60 (50%)         45/60 (75%)             |
|ADJUSTED (b)           |         74.4%               88.2%                  |         61.0%               88.2%                  |
|INTERIM SACRIFICE 1 (c)|         1/10 (10%)          1/10 (10%)             |         1/10 (10%)          2/9 (22%)              |
|TERMINAL (d)           |        30/43 (70%)         33/39 (85%)             |        21/40 (53%)         32/38 (84%)             |
|FIRST INCIDENCE (DAYS) |          440                 463 (I)               |          463 (I)             463 (I)               |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                             P=0.053                |                             P=0.006 **             |
|INCIDENTAL TUMOR       |                             P=0.107                |                             P=0.004 **             |
|LOGISTIC REGRESSION    |                             P=0.143                |                             P=0.003 **             |
|COCHRAN-ARMITAGE       |                                                    |                                                    |
|FISHER EXACT           |                             P=0.118                |                             P=0.004 **             |
|=================================================================================================================================|
 
 (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):   463
          Female interim sacrifices(days): 463
 (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.