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TDMS Study 05063-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                                   PHENYLBUTAZONE                                    DATE: 09/08/94       
EXPERIMENT: 05063 TEST: 01                                                                                     TIME: 19:32:24       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-28033          ROUTE: GAVAGE                                                                      NTP C#: 56531        
PATHOLOGIST: R. FLEISCHMAN                                                                                     CAS: 50-33-9         
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Mason                                                   PHENYLBUTAZONE                                    DATE: 09/08/94      
EXPERIMENT: 05063 TEST: 01                                                                                     TIME: 19:32:24      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-28033          ROUTE: GAVAGE                                                                      NTP C#: 56531       
PATHOLOGIST: R. FLEISCHMAN                                                                                     CAS: 50-33-9        
 
 
 
 
 
                                                    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: Mason                                                   PHENYLBUTAZONE                                    DATE: 09/08/94       
EXPERIMENT: 05063 TEST: 01                                                                                     TIME: 19:32:24       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-28033          ROUTE: GAVAGE                                                                      NTP C#: 56531        
PATHOLOGIST: R. FLEISCHMAN                                                                                     CAS: 50-33-9         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                         IN THE ANALYSIS OF THE STUDY OF PHENYLBUTAZONE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma or Adenoma
                             Islets, Pancreatic            Carcinoma or Adenoma
                             Kidney: Renal Tubule          Adenoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                             Urinary Bladder               Papilloma
                             All Organs                    Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             Mammary Gland                 Fibroadenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                             Uterus                        Polyp Stromal
                                                           Sarcoma Stromal or Polyp Stromal
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   1
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    16/50 (32%)     18/49 (37%)     19/49 (39%)     |     3/50 (6%)       1/50 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |     42.9%           67.4%           54.7%          |      8.8%            2.9%            9.1%          |
|TERMINAL (d)           |    12/33 (36%)     11/19 (58%)     11/26 (42%)     |     2/31 (6%)       1/35 (3%)       2/22 (9%)      |
|FIRST INCIDENCE (DAYS) |      618             536             658           |      637             732 (T)         732 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.141         P=0.035 *       P=0.177        |     P=0.517N        P=0.269N        P=0.643N       |
|INCIDENTAL TUMOR       |     P=0.315         P=0.172         P=0.412        |     P=0.453N        P=0.317N        P=0.573N       |
|LOGISTIC REGRESSION    |     P=0.228         P=0.146         P=0.354        |     P=0.464N        P=0.294N        P=0.581N       |
|COCHRAN-ARMITAGE       |     P=0.275                                        |     P=0.399N                                       |
|FISHER EXACT           |                     P=0.388         P=0.310        |                     P=0.309N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Complex                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/49 (0%)       2/49 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      3.0%            0.0%            6.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/19 (0%)       1/26 (4%)      |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         ---             567           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.319         P=0.610N        P=0.440        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.317         P=0.610N        P=0.445        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.356         P=0.610N        P=0.496        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.356                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.505N        P=0.492        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   2
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       2/49 (4%)       2/49 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     10.5%            8.6%            5.6%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       1/19 (5%)       0/26 (0%)      |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      618             654             692           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.288N        P=0.507N        P=0.355N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.142N        P=0.246N        P=0.187N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.225N        P=0.367N        P=0.349N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.260N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.349N        P=0.349N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    19/50 (38%)     20/49 (41%)     21/49 (43%)     |     3/50 (6%)       1/50 (2%)       3/50 (6%)      |
|ADJUSTED (b)           |     49.6%           72.5%           58.6%          |      8.8%            2.9%           13.6%          |
|TERMINAL (d)           |    14/33 (42%)     12/19 (63%)     12/26 (46%)     |     2/31 (6%)       1/35 (3%)       3/22 (14%)     |
|FIRST INCIDENCE (DAYS) |      618             536             567           |      637             732 (T)         732 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.179         P=0.040 *       P=0.221        |     P=0.464         P=0.269N        P=0.507        |
|INCIDENTAL TUMOR       |     P=0.389         P=0.224         P=0.471        |     P=0.525         P=0.317N        P=0.575        |
|LOGISTIC REGRESSION    |     P=0.298         P=0.186         P=0.342        |     P=0.518         P=0.294N        P=0.572        |
|COCHRAN-ARMITAGE       |     P=0.348                                        |     P=0.593N                                       |
|FISHER EXACT           |                     P=0.468         P=0.387        |                     P=0.309N        P=0.661N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   3
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/43 (5%)       4/25 (16%)      0/47 (0%)      |     5/36 (14%)      4/11 (36%)      0/41 (0%)      |
|ADJUSTED (b)           |      6.3%           51.1%            0.0%          |     20.8%           51.3%            0.0%          |
|TERMINAL (d)           |     2/32 (6%)       3/6 (50%)       0/27 (0%)      |     5/24 (21%)      3/6 (50%)       0/18 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         536             ---           |      732 (T)         683             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.308N        P=0.008 **      P=0.276N       |     P=0.089N        P=0.108         P=0.059N       |
|INCIDENTAL TUMOR       |     P=0.319N        P=0.012 *       P=0.276N       |     P=0.066N        P=0.076         P=0.059N       |
|LOGISTIC REGRESSION    |     P=0.222N        P=0.026 *       P=0.276N       |     P=0.055N        P=0.072         P=0.059N       |
|COCHRAN-ARMITAGE       |     P=0.210N                                       |     P=0.030N*                                      |
|FISHER EXACT           |                     P=0.127         P=0.225N       |                     P=0.114         P=0.019N*      |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/43 (0%)       1/25 (4%)       2/47 (4%)      |     0/36 (0%)       2/11 (18%)      2/41 (5%)      |
|ADJUSTED (b)           |      0.0%            4.2%            6.3%          |      0.0%           33.3%            7.0%          |
|TERMINAL (d)           |     0/32 (0%)       0/6 (0%)        1/27 (4%)      |     0/24 (0%)       2/6 (33%)       0/18 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             704             689           |      ---             732 (T)         673           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.158         P=0.436         P=0.230        |     P=0.133         P=0.024 *       P=0.189        |
|INCIDENTAL TUMOR       |     P=0.321         P=0.227         P=0.321        |     P=0.283         P=0.024 *       P=0.454        |
|LOGISTIC REGRESSION    |     P=0.180         P=0.269         P=0.251        |     P=0.202         P=0.024 *       P=0.251        |
|COCHRAN-ARMITAGE       |     P=0.178                                        |     P=0.242                                        |
|FISHER EXACT           |                     P=0.368         P=0.270        |                     P=0.051         P=0.280        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   4
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/43 (5%)       5/25 (20%)      2/47 (4%)      |     5/36 (14%)      6/11 (55%)      2/41 (5%)      |
|ADJUSTED (b)           |      6.3%           53.1%            6.3%          |     20.8%           83.8%            7.0%          |
|TERMINAL (d)           |     2/32 (6%)       3/6 (50%)       1/27 (4%)      |     5/24 (21%)      5/6 (83%)       0/18 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         536             689           |      732 (T)         683             673           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.509         P=0.004 **      P=0.656        |     P=0.366N        P=0.005 **      P=0.339N       |
|INCIDENTAL TUMOR       |     P=0.528N        P=0.002 **      P=0.660N       |     P=0.213N        P=0.003 **      P=0.189N       |
|LOGISTIC REGRESSION    |     P=0.544N        P=0.005 **      P=0.685N       |     P=0.237N        P=0.003 **      P=0.230N       |
|COCHRAN-ARMITAGE       |     P=0.530N                                       |     P=0.149N                                       |
|FISHER EXACT           |                     P=0.058         P=0.657N       |                     P=0.011 *       P=0.165N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/22 (5%)       0/50 (0%)      |     0/50 (0%)       0/7 (0%)        0/50 (0%)      |
|ADJUSTED (b)           |      6.1%           50.0%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/33 (6%)       1/2 (50%)       0/27 (0%)      |     0/31 (0%)       0/0             0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.235N        P=0.200         P=0.283N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.235N        P=0.200         P=0.283N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.235N        P=0.200         P=0.283N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.167N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.671         P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   5
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/22 (0%)       0/50 (0%)      |     0/50 (0%)       0/7 (0%)        0/50 (0%)      |
|ADJUSTED (b)           |      6.1%            0.0%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/33 (6%)       0/2 (0%)        0/27 (0%)      |     0/31 (0%)       0/0             0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         ---             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.171N        P=0.884N        P=0.283N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.171N        P=0.884N        P=0.283N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.171N        P=0.884N        P=0.283N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.119N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.479N        P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       1/22 (5%)       0/50 (0%)      |     0/50 (0%)       0/7 (0%)        0/50 (0%)      |
|ADJUSTED (b)           |     12.1%           50.0%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     4/33 (12%)      1/2 (50%)       0/27 (0%)      |     0/31 (0%)       0/0             0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.077N        P=0.330         P=0.090N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.077N        P=0.330         P=0.090N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.077N        P=0.330         P=0.090N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.039N*                                      |       (e)                                          |
|FISHER EXACT           |                     P=0.514N        P=0.059N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   6
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Pelvis and Transitional Epithelium                                                                                       |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/49 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      0.0%            0.0%            7.0%          |
|TERMINAL (d)           |     0/33 (0%)       0/20 (0%)       0/27 (0%)      |     0/31 (0%)       0/35 (0%)       1/22 (5%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      ---             ---             578           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.071           (e)           P=0.193        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.121           (e)           P=0.260        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.099           (e)           P=0.240        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.096                                        |
|FISHER EXACT           |                       (e)             (e)          |                       (e)           P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/49 (0%)       3/50 (6%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%           10.5%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/33 (0%)       0/20 (0%)       2/27 (7%)      |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             716           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.035 *         (e)           P=0.095        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.046 *         (e)           P=0.138        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.040 *         (e)           P=0.111        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.038 *                                      |       (e)                                          |
|FISHER EXACT           |                       (e)           P=0.121        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   7
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/49 (2%)       3/50 (6%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            5.0%           10.5%          |      0.0%            2.9%            0.0%          |
|TERMINAL (d)           |     0/33 (0%)       1/20 (5%)       2/27 (7%)      |     0/31 (0%)       1/35 (3%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         716           |      ---             732 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.053         P=0.400         P=0.095        |     P=0.697         P=0.524           (e)          |
|INCIDENTAL TUMOR       |     P=0.067         P=0.400         P=0.138        |     P=0.697         P=0.524           (e)          |
|LOGISTIC REGRESSION    |     P=0.061         P=0.400         P=0.111        |     P=0.697         P=0.524           (e)          |
|COCHRAN-ARMITAGE       |     P=0.061                                        |     P=0.730                                        |
|FISHER EXACT           |                     P=0.495         P=0.121        |                     P=0.500           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |     1/50 (2%)       2/27 (7%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            2.8%            3.7%          |      3.2%            8.8%            0.0%          |
|TERMINAL (d)           |     0/33 (0%)       0/20 (0%)       1/27 (4%)      |     1/31 (3%)       1/15 (7%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             620             730 (T)       |      732 (T)         655             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.316         P=0.479         P=0.460        |     P=0.454N        P=0.350         P=0.568N       |
|INCIDENTAL TUMOR       |     P=0.306         P=0.612         P=0.460        |     P=0.416N        P=0.285         P=0.568N       |
|LOGISTIC REGRESSION    |     P=0.331         P=0.548         P=0.460        |     P=0.413N        P=0.268         P=0.568N       |
|COCHRAN-ARMITAGE       |     P=0.332                                        |     P=0.372N                                       |
|FISHER EXACT           |                     P=0.500         P=0.500        |                     P=0.280         P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   8
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/34 (9%)       0/50 (0%)      |     1/50 (2%)       0/20 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%           17.3%            0.0%          |      3.2%            0.0%            7.9%          |
|TERMINAL (d)           |     0/33 (0%)       1/9 (11%)       0/27 (0%)      |     1/31 (3%)       0/10 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             616             ---           |      732 (T)         ---             703           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.590         P=0.042 *         (e)          |     P=0.287         P=0.725N        P=0.400        |
|INCIDENTAL TUMOR       |     P=0.580N        P=0.067           (e)          |     P=0.386         P=0.725N        P=0.512        |
|LOGISTIC REGRESSION    |     P=0.626         P=0.028 *         (e)          |     P=0.309         P=0.725N        P=0.423        |
|COCHRAN-ARMITAGE       |     P=0.631                                        |     P=0.375                                        |
|FISHER EXACT           |                     P=0.063           (e)          |                     P=0.714N        P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/34 (0%)       0/50 (0%)      |     0/50 (0%)       0/20 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      6.1%            0.0%            0.0%          |      0.0%            0.0%            4.2%          |
|TERMINAL (d)           |     2/33 (6%)       0/9 (0%)        0/27 (0%)      |     0/31 (0%)       0/10 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         ---             ---           |      ---             ---             721           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.155N        P=0.550N        P=0.283N       |     P=0.226           (e)           P=0.443        |
|INCIDENTAL TUMOR       |     P=0.155N        P=0.550N        P=0.283N       |     P=0.331           (e)           P=0.545        |
|LOGISTIC REGRESSION    |     P=0.155N        P=0.550N        P=0.283N       |     P=0.257           (e)           P=0.456        |
|COCHRAN-ARMITAGE       |     P=0.108N                                       |     P=0.292                                        |
|FISHER EXACT           |                     P=0.351N        P=0.247N       |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE   9
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       3/34 (9%)       0/50 (0%)      |     1/50 (2%)       0/20 (0%)       3/50 (6%)      |
|ADJUSTED (b)           |      6.1%           17.3%            0.0%          |      3.2%            0.0%           11.7%          |
|TERMINAL (d)           |     2/33 (6%)       1/9 (11%)       0/27 (0%)      |     1/31 (3%)       0/10 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         616             ---           |      732 (T)         ---             703           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.278N        P=0.162         P=0.283N       |     P=0.123         P=0.725N        P=0.213        |
|INCIDENTAL TUMOR       |     P=0.214N        P=0.214         P=0.283N       |     P=0.221         P=0.725N        P=0.329        |
|LOGISTIC REGRESSION    |     P=0.231N        P=0.151         P=0.283N       |     P=0.147         P=0.725N        P=0.228        |
|COCHRAN-ARMITAGE       |     P=0.215N                                       |     P=0.202                                        |
|FISHER EXACT           |                     P=0.322         P=0.247N       |                     P=0.714N        P=0.309        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       5/50 (10%)      3/50 (6%)      |    22/50 (44%)     15/50 (30%)      7/50 (14%)     |
|ADJUSTED (b)           |      5.1%           20.0%           11.1%          |     62.5%           36.0%           24.7%          |
|TERMINAL (d)           |     1/33 (3%)       2/20 (10%)      3/27 (11%)     |    18/31 (58%)      9/35 (26%)      3/22 (14%)     |
|FIRST INCIDENCE (DAYS) |      526             623             730 (T)       |      485             578             590           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.348         P=0.108         P=0.425        |     P=0.010N*       P=0.057N        P=0.017N*      |
|INCIDENTAL TUMOR       |     P=0.426         P=0.250         P=0.427        |     P=0.001N**      P=0.076N        P=0.003N**     |
|LOGISTIC REGRESSION    |     P=0.414         P=0.193         P=0.499        |     P=0.002N**      P=0.076N        P=0.003N**     |
|COCHRAN-ARMITAGE       |     P=0.420                                        |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.218         P=0.500        |                     P=0.107N        P<0.001N**     |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  10
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       5/50 (10%)      3/50 (6%)      |    23/50 (46%)     15/50 (30%)      7/50 (14%)     |
|ADJUSTED (b)           |      5.1%           20.0%           11.1%          |     63.6%           36.0%           24.7%          |
|TERMINAL (d)           |     1/33 (3%)       2/20 (10%)      3/27 (11%)     |    18/31 (58%)      9/35 (26%)      3/22 (14%)     |
|FIRST INCIDENCE (DAYS) |      526             623             730 (T)       |      485             578             590           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.348         P=0.108         P=0.425        |     P=0.007N**      P=0.041N*       P=0.012N*      |
|INCIDENTAL TUMOR       |     P=0.426         P=0.250         P=0.427        |     P<0.001N**      P=0.049N*       P=0.002N**     |
|LOGISTIC REGRESSION    |     P=0.414         P=0.193         P=0.499        |     P<0.001N**      P=0.051N        P=0.002N**     |
|COCHRAN-ARMITAGE       |     P=0.420                                        |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.218         P=0.500        |                     P=0.074N        P<0.001N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       3/27 (11%)      4/50 (8%)      |     1/50 (2%)       0/9 (0%)        0/50 (0%)      |
|ADJUSTED (b)           |      9.1%           41.4%           14.8%          |      3.0%            0.0%            0.0%          |
|TERMINAL (d)           |     3/33 (9%)       2/5 (40%)       4/27 (15%)     |     0/31 (0%)       0/0             0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         542             730 (T)       |      714             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.317         P=0.060         P=0.390        |     P=0.299N        P=0.488N        P=0.555N       |
|INCIDENTAL TUMOR       |     P=0.316         P=0.076         P=0.390        |     P=0.263N        P=0.773N        P=0.455N       |
|LOGISTIC REGRESSION    |     P=0.413         P=0.116         P=0.390        |     P=0.338N        P=0.988N        P=0.537N       |
|COCHRAN-ARMITAGE       |     P=0.426                                        |     P=0.300N                                       |
|FISHER EXACT           |                     P=0.351         P=0.500        |                     P=0.847N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  11
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    16/48 (33%)     10/26 (38%)     21/47 (45%)     |    30/48 (63%)     24/49 (49%)     22/50 (44%)     |
|ADJUSTED (b)           |     44.2%          100.0%           59.7%          |     78.3%           61.3%           64.7%          |
|TERMINAL (d)           |    12/31 (39%)      4/4 (100%)     12/25 (48%)     |    22/30 (73%)     20/35 (57%)     11/22 (50%)     |
|FIRST INCIDENCE (DAYS) |      521             623             564           |      485             557             504           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.073         P=0.038 *       P=0.092        |     P=0.404N        P=0.048N*       P=0.490N       |
|INCIDENTAL TUMOR       |     P=0.159         P=0.073         P=0.152        |     P=0.082N        P=0.093N        P=0.098N       |
|LOGISTIC REGRESSION    |     P=0.143         P=0.052         P=0.174        |     P=0.087N        P=0.080N        P=0.099N       |
|COCHRAN-ARMITAGE       |     P=0.152                                        |     P=0.042N*                                      |
|FISHER EXACT           |                     P=0.423         P=0.178        |                     P=0.128N        P=0.051N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.3%            4.8%            2.9%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/20 (0%)       0/27 (0%)      |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      599             728             703           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.422N        P=0.619N        P=0.528N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.279N        P=0.426N        P=0.435N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.383N        P=0.527N        P=0.498N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.378N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  12
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       2/50 (4%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.3%            7.6%            5.6%          |      0.0%            2.9%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/20 (0%)       0/27 (0%)      |     0/31 (0%)       1/35 (3%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      599             623             692           |      ---             732 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.568         P=0.581         P=0.675        |     P=0.697         P=0.524           (e)          |
|INCIDENTAL TUMOR       |     P=0.469N        P=0.586N        P=0.573N       |     P=0.697         P=0.524           (e)          |
|LOGISTIC REGRESSION    |     P=0.599         P=0.698         P=0.694N       |     P=0.697         P=0.524           (e)          |
|COCHRAN-ARMITAGE       |     P=0.601                                        |     P=0.730                                        |
|FISHER EXACT           |                     P=0.691N        P=0.691N       |                     P=0.500           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       3/50 (6%)       4/50 (8%)      |     1/50 (2%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      7.1%            8.3%           13.3%          |      3.2%            2.9%            2.4%          |
|TERMINAL (d)           |     1/33 (3%)       0/20 (0%)       3/27 (11%)     |     1/31 (3%)       1/35 (3%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      521             536             598           |      732 (T)         732 (T)         527           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.372         P=0.581         P=0.429        |     P=0.580         P=0.735N        P=0.715        |
|INCIDENTAL TUMOR       |     P=0.409         P=0.515N        P=0.438        |     P=0.634N        P=0.735N        P=0.751N       |
|LOGISTIC REGRESSION    |     P=0.429         P=0.506N        P=0.515        |     P=0.636N        P=0.735N        P=0.749N       |
|COCHRAN-ARMITAGE       |     P=0.421                                        |     P=0.640                                        |
|FISHER EXACT           |                     P=0.661N        P=0.500        |                     P=0.753N        P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  13
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.0%            0.0%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/20 (0%)       0/27 (0%)      |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      456             ---             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.116N        P=0.302N        P=0.262N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.107N        P=0.244N        P=0.262N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.075N        P=0.150N        P=0.220N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.095N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.247N        P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       3/50 (6%)       4/50 (8%)      |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      8.9%            8.3%           13.3%          |      5.2%            2.9%            2.4%          |
|TERMINAL (d)           |     1/33 (3%)       0/20 (0%)       3/27 (11%)     |     1/31 (3%)       1/35 (3%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      456             536             598           |      421             732 (T)         527           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.520         P=0.581N        P=0.576        |     P=0.433N        P=0.479N        P=0.550N       |
|INCIDENTAL TUMOR       |     P=0.570         P=0.315N        P=0.590        |     P=0.333N        P=0.634N        P=0.430N       |
|LOGISTIC REGRESSION    |     P=0.565N        P=0.268N        P=0.622N       |     P=0.338N        P=0.505N        P=0.437N       |
|COCHRAN-ARMITAGE       |     P=0.576N                                       |     P=0.378N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.643N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  14
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.0%            0.0%            0.0%          |      2.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/20 (0%)       0/27 (0%)      |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      456             ---             ---           |      421             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.116N        P=0.302N        P=0.262N       |     P=0.275N        P=0.513N        P=0.504N       |
|INCIDENTAL TUMOR       |     P=0.107N        P=0.244N        P=0.262N       |     P=0.224N        P=0.814N        P=0.406N       |
|LOGISTIC REGRESSION    |     P=0.075N        P=0.150N        P=0.220N       |     P=0.208N        P=0.508N        P=0.422N       |
|COCHRAN-ARMITAGE       |     P=0.095N                                       |     P=0.270N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.247N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    46/50 (92%)     41/49 (84%)     48/50 (96%)     |                                                    |
|ADJUSTED (b)           |     93.9%           95.1%          100.0%          |                                                    |
|TERMINAL (d)           |    30/33 (91%)     18/20 (90%)     27/27 (100%)    |                                                    |
|FIRST INCIDENCE (DAYS) |      456             381             494           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.127         P=0.077         P=0.129        |                                                    |
|INCIDENTAL TUMOR       |     P=0.282         P=0.249N        P=0.385        |                                                    |
|LOGISTIC REGRESSION    |     P=0.275         P=0.270N        P=0.319        |                                                    |
|COCHRAN-ARMITAGE       |     P=0.305                                        |                                                    |
|FISHER EXACT           |                     P=0.168N        P=0.339        |                                                    |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  15
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/49 (12%)      1/21 (5%)       2/49 (4%)      |     2/50 (4%)       4/49 (8%)       0/50 (0%)      |
|ADJUSTED (b)           |     17.9%            2.9%            7.7%          |      4.8%           10.6%            0.0%          |
|TERMINAL (d)           |     5/32 (16%)      0/1 (0%)        2/26 (8%)      |     0/31 (0%)       3/35 (9%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      672             622             730 (T)       |      619             619             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.155N        P=0.724N        P=0.198N       |     P=0.302N        P=0.381         P=0.289N       |
|INCIDENTAL TUMOR       |     P=0.124N        P=0.673         P=0.159N       |     P=0.164N        P=0.239         P=0.114N       |
|LOGISTIC REGRESSION    |     P=0.110N        P=0.696         P=0.143N       |     P=0.228N        P=0.327         P=0.220N       |
|COCHRAN-ARMITAGE       |     P=0.091N                                       |     P=0.224N                                       |
|FISHER EXACT           |                     P=0.317N        P=0.134N       |                     P=0.329         P=0.247N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/49 (14%)      2/21 (10%)      2/49 (4%)      |     3/50 (6%)       5/49 (10%)      0/50 (0%)      |
|ADJUSTED (b)           |     20.9%            5.1%            7.7%          |      7.9%           13.4%            0.0%          |
|TERMINAL (d)           |     6/32 (19%)      0/1 (0%)        2/26 (8%)      |     1/31 (3%)       4/35 (11%)      0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      672             577             730 (T)       |      619             619             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.111N        P=0.519         P=0.130N       |     P=0.206N        P=0.412         P=0.174N       |
|INCIDENTAL TUMOR       |     P=0.085N        P=0.459         P=0.102N       |     P=0.111N        P=0.288         P=0.071N       |
|LOGISTIC REGRESSION    |     P=0.070N        P=0.487         P=0.087N       |     P=0.147N        P=0.349         P=0.118N       |
|COCHRAN-ARMITAGE       |     P=0.058N                                       |     P=0.134N                                       |
|FISHER EXACT           |                     P=0.455N        P=0.080N       |                     P=0.346         P=0.121N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  16
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       0/21 (0%)       1/49 (2%)      |     0/50 (0%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      6.0%            0.0%            3.8%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/32 (3%)       0/1 (0%)        1/26 (4%)      |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      701             ---             730 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.428N        P=0.543N        P=0.548N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.344N        P=0.997N        P=0.460N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.395N        P=0.850N        P=0.512N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.374N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.487N        P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Papilloma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/45 (0%)       2/22 (9%)       0/48 (0%)      |     0/50 (0%)       1/49 (2%)       0/49 (0%)      |
|ADJUSTED (b)           |      0.0%           51.3%            0.0%          |      0.0%            2.9%            0.0%          |
|TERMINAL (d)           |     0/28 (0%)       1/2 (50%)       0/25 (0%)      |     0/31 (0%)       1/35 (3%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             597             ---           |      ---             732 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.628         P=0.043 *         (e)          |     P=0.697         P=0.524           (e)          |
|INCIDENTAL TUMOR       |     P=0.641         P=0.068           (e)          |     P=0.697         P=0.524           (e)          |
|LOGISTIC REGRESSION    |     P=0.640N        P=0.039 *         (e)          |     P=0.698         P=0.524           (e)          |
|COCHRAN-ARMITAGE       |     P=0.640N                                       |     P=0.727                                        |
|FISHER EXACT           |                     P=0.104           (e)          |                     P=0.495           (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  17
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    16/50 (32%)      7/50 (14%)     12/50 (24%)     |
|ADJUSTED (b)           |                                                    |     40.8%           20.0%           38.3%          |
|TERMINAL (d)           |                                                    |     9/31 (29%)      7/35 (20%)      5/22 (23%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      485             732 (T)         508           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.446N        P=0.019N*       P=0.552N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.207N        P=0.043N*       P=0.238N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.241N        P=0.026N*       P=0.290N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.203N                                       |
|FISHER EXACT           |                                                    |                     P=0.028N*       P=0.252N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     2/50 (4%)       3/50 (6%)       0/50 (0%)      |
|ADJUSTED (b)           |                                                    |      5.5%            6.3%            0.0%          |
|TERMINAL (d)           |                                                    |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      651             359             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.230N        P=0.514         P=0.293N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.126N        P=0.419         P=0.185N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.141N        P=0.505         P=0.247N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.202N                                       |
|FISHER EXACT           |                                                    |                     P=0.500         P=0.247N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  18
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    18/50 (36%)     10/50 (20%)     12/50 (24%)     |
|ADJUSTED (b)           |                                                    |     44.1%           25.0%           38.3%          |
|TERMINAL (d)           |                                                    |     9/31 (29%)      7/35 (20%)      5/22 (23%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      485             359             508           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.302N        P=0.047N*       P=0.412N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.086N        P=0.099N        P=0.114N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.104N        P=0.062N        P=0.165N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.107N                                       |
|FISHER EXACT           |                                                    |                     P=0.059N        P=0.138N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      5.2%            2.6%            3.7%          |      0.0%            0.0%            4.4%          |
|TERMINAL (d)           |     1/33 (3%)       0/20 (0%)       1/27 (4%)      |     0/31 (0%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      598             607             730 (T)       |      ---             ---             508           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.425N        P=0.579N        P=0.555N       |     P=0.095           (e)           P=0.237        |
|INCIDENTAL TUMOR       |     P=0.412N        P=0.428N        P=0.546N       |     P=0.201           (e)           P=0.341        |
|LOGISTIC REGRESSION    |     P=0.376N        P=0.459N        P=0.500N       |     P=0.124           (e)           P=0.287        |
|COCHRAN-ARMITAGE       |     P=0.378N                                       |     P=0.096                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                       (e)           P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  19
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       2/50 (4%)      |    11/50 (22%)      6/50 (12%)      4/50 (8%)      |
|ADJUSTED (b)           |      5.0%            8.3%            5.7%          |     26.9%           15.0%           18.2%          |
|TERMINAL (d)           |     0/33 (0%)       1/20 (5%)       1/27 (4%)      |     3/31 (10%)      3/35 (9%)       4/22 (18%)     |
|FIRST INCIDENCE (DAYS) |      589             646             505           |      504             557             732 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.565         P=0.582         P=0.669        |     P=0.086N        P=0.119N        P=0.147N       |
|INCIDENTAL TUMOR       |     P=0.535N        P=0.584N        P=0.644N       |     P=0.022N*       P=0.200N        P=0.040N*      |
|LOGISTIC REGRESSION    |     P=0.598N        P=0.688N        P=0.682N       |     P=0.035N*       P=0.236N        P=0.057N       |
|COCHRAN-ARMITAGE       |     P=0.601                                        |     P=0.030N*                                      |
|FISHER EXACT           |                     P=0.691N        P=0.691N       |                     P=0.143N        P=0.045N*      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       4/50 (8%)       3/50 (6%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      7.5%           17.0%            7.6%          |      3.2%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       3/20 (15%)      1/27 (4%)      |     1/31 (3%)       0/35 (0%)       0/22 (0%)      |
|FIRST INCIDENCE (DAYS) |      598             584             494           |      732 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.508         P=0.326         P=0.621        |     P=0.303N        P=0.476N        P=0.568N       |
|INCIDENTAL TUMOR       |     P=0.520         P=0.474         P=0.633        |     P=0.303N        P=0.476N        P=0.568N       |
|LOGISTIC REGRESSION    |     P=0.574N        P=0.488         P=0.642N       |     P=0.303N        P=0.476N        P=0.568N       |
|COCHRAN-ARMITAGE       |     P=0.579                                        |     P=0.270N                                       |
|FISHER EXACT           |                     P=0.500         P=0.661N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  20
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    49/50 (98%)     47/50 (94%)     49/50 (98%)     |    43/50 (86%)     39/50 (78%)     35/50 (70%)     |
|ADJUSTED (b)           |     98.0%          100.0%          100.0%          |     97.7%           86.6%           83.0%          |
|TERMINAL (d)           |    32/33 (97%)     20/20 (100%)    27/27 (100%)    |    30/31 (97%)     29/35 (83%)     15/22 (68%)     |
|FIRST INCIDENCE (DAYS) |      456             381             494           |      485             299             504           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.188         P=0.019 *       P=0.198        |     P=0.398         P=0.086N        P=0.397        |
|INCIDENTAL TUMOR       |     P=0.610N        P=0.538N        P=0.738N       |     P=0.062N        P=0.154N        P=0.075N       |
|LOGISTIC REGRESSION    |     P=0.617         P=0.642N        P=0.757        |     P=0.073N        P=0.175N        P=0.094N       |
|COCHRAN-ARMITAGE       |     P=0.609N                                       |     P=0.035N*                                      |
|FISHER EXACT           |                     P=0.309N        P=0.753N       |                     P=0.218N        P=0.045N*      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    21/50 (42%)     14/50 (28%)     15/50 (30%)     |    19/50 (38%)     16/50 (32%)     12/50 (24%)     |
|ADJUSTED (b)           |     48.4%           44.9%           38.1%          |     42.9%           38.1%           39.7%          |
|TERMINAL (d)           |    11/33 (33%)      6/20 (30%)      6/27 (22%)     |     6/31 (19%)     10/35 (29%)      6/22 (27%)     |
|FIRST INCIDENCE (DAYS) |      456             448             494           |      421             359             508           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.254N        P=0.498N        P=0.278N       |     P=0.285N        P=0.264N        P=0.343N       |
|INCIDENTAL TUMOR       |     P=0.077N        P=0.072N        P=0.078N       |     P=0.049N*       P=0.458N        P=0.050N*      |
|LOGISTIC REGRESSION    |     P=0.118N        P=0.109N        P=0.138N       |     P=0.077N        P=0.348N        P=0.104N       |
|COCHRAN-ARMITAGE       |     P=0.121N                                       |     P=0.081N                                       |
|FISHER EXACT           |                     P=0.104N        P=0.149N       |                     P=0.338N        P=0.097N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 01                                                 PAGE  21
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.05G/KG        0.1 G/KG      |      VEHICLE         0.05G/KG        0.1 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    50/50 (100%)    48/50 (96%)     50/50 (100%)    |    46/50 (92%)     46/50 (92%)     36/50 (72%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     97.9%           93.9%           85.4%          |
|TERMINAL (d)           |    33/33 (100%)    20/20 (100%)    27/27 (100%)    |    30/31 (97%)     32/35 (91%)     16/22 (73%)     |
|FIRST INCIDENCE (DAYS) |      456             381             494           |      421             299             504           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.186         P=0.017 *       P=0.192        |     P=0.488         P=0.263N        P=0.501        |
|INCIDENTAL TUMOR       |     P=0.746N        P=0.581N          (e)          |     P=0.006N**      P=0.606         P=0.012N*      |
|LOGISTIC REGRESSION    |     P=0.765N        P=0.639N          (e)          |     P=0.007N**      P=0.647N        P=0.018N*      |
|COCHRAN-ARMITAGE       |     P=0.668N                                       |     P=0.004N**                                     |
|FISHER EXACT           |                     P=0.247N        P=1.000N       |                     P=0.643N        P=0.009N**     |
|=================================================================================================================================|
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (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.