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TDMS Study 05063-02 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                                   PHENYLBUTAZONE                                    DATE: 09/08/94       
EXPERIMENT: 05063 TEST: 02                                                                                     TIME: 21:23:06       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01ES1803301          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: 02                                                                                     TIME: 21:23:06      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01ES1803301          ROUTE: GAVAGE                                                                      NTP C#: 56531       
PATHOLOGIST: R. FLEISCHMAN                                                                                     CAS: 50-33-9        
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                                   PHENYLBUTAZONE                                    DATE: 09/08/94       
EXPERIMENT: 05063 TEST: 02                                                                                     TIME: 21:23:06       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES1803301          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 MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Skin: Subcutaneous Tissue     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, or Sarcoma
                             All Organs                    Malignant Lymphoma And Histiocytic Sarcoma
                                                           Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,
                                                            NOS, or Undifferentiated Cell Type
                                                           Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Stomach, Forestomach          Squamous Cell Carcinoma or Papilloma Squamous
                             All Organs                    Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   1
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.6%            2.5%            2.8%          |      3.6%            0.0%            0.0%          |
|TERMINAL (d)           |     2/36 (6%)       1/40 (3%)       1/36 (3%)      |     0/22 (0%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         730 (T)       |      710             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.376N        P=0.463N        P=0.500N       |     P=0.249N        P=0.486N        P=0.467N       |
|INCIDENTAL TUMOR       |     P=0.376N        P=0.463N        P=0.500N       |     P=0.451N        P=0.718N        P=0.718N       |
|LOGISTIC REGRESSION    |     P=0.376N        P=0.463N        P=0.500N       |     P=0.273N        P=0.513N        P=0.504N       |
|COCHRAN-ARMITAGE       |     P=0.378N                                       |     P=0.270N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |     0/50 (0%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            4.6%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       1/40 (3%)       0/36 (0%)      |     0/22 (0%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             627             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.664         P=0.256           (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.615         P=0.176           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.668N        P=0.242           (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.668                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.247           (e)          |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   2
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     8/50 (16%)     12/50 (24%)     24/50 (48%)     |     4/50 (8%)       5/49 (10%)      7/50 (14%)     |
|ADJUSTED (b)           |     20.0%           29.1%           61.1%          |     16.4%           17.2%           21.9%          |
|TERMINAL (d)           |     5/36 (14%)     11/40 (28%)     21/36 (58%)     |     3/22 (14%)      5/29 (17%)      7/32 (22%)     |
|FIRST INCIDENCE (DAYS) |      627             647             500           |      688             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.306         P<0.001 **     |     P=0.414         P=0.625N        P=0.490        |
|INCIDENTAL TUMOR       |     P<0.001 **      P=0.228         P<0.001 **     |     P=0.355         P=0.586         P=0.413        |
|LOGISTIC REGRESSION    |     P<0.001 **      P=0.231         P<0.001 **     |     P=0.303         P=0.532         P=0.356        |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P=0.210                                        |
|FISHER EXACT           |                     P=0.227         P<0.001 **     |                     P=0.487         P=0.262        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     8/50 (16%)      4/50 (8%)      11/50 (22%)     |     1/50 (2%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     18.3%           10.0%           25.1%          |      4.5%            0.0%            0.0%          |
|TERMINAL (d)           |     3/36 (8%)       4/40 (10%)      4/36 (11%)     |     1/22 (5%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      440             730 (T)         500           |      731 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.248         P=0.157N        P=0.310        |     P=0.218N        P=0.445N        P=0.425N       |
|INCIDENTAL TUMOR       |     P=0.265         P=0.331N        P=0.287        |     P=0.218N        P=0.445N        P=0.425N       |
|LOGISTIC REGRESSION    |     P=0.252         P=0.165N        P=0.355        |     P=0.218N        P=0.445N        P=0.425N       |
|COCHRAN-ARMITAGE       |     P=0.245                                        |     P=0.270N                                       |
|FISHER EXACT           |                     P=0.178N        P=0.306        |                     P=0.505N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   3
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    16/50 (32%)     14/50 (28%)     31/50 (62%)     |     5/50 (10%)      5/49 (10%)      7/50 (14%)     |
|ADJUSTED (b)           |     35.6%           34.0%           70.3%          |     20.8%           17.2%           21.9%          |
|TERMINAL (d)           |     8/36 (22%)     13/40 (33%)     23/36 (64%)     |     4/22 (18%)      5/29 (17%)      7/32 (22%)     |
|FIRST INCIDENCE (DAYS) |      440             647             500           |      688             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.003 **      P=0.326N        P=0.007 **     |     P=0.564         P=0.466N        P=0.613N       |
|INCIDENTAL TUMOR       |     P=0.001 **      P=0.564N        P=0.002 **     |     P=0.504         P=0.537N        P=0.570        |
|LOGISTIC REGRESSION    |     P=0.001 **      P=0.421N        P=0.002 **     |     P=0.441         P=0.599N        P=0.502        |
|COCHRAN-ARMITAGE       |     P=0.002 **                                     |     P=0.319                                        |
|FISHER EXACT           |                     P=0.414N        P=0.002 **     |                     P=0.617         P=0.380        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    16/50 (32%)     14/50 (28%)     31/50 (62%)     |     5/50 (10%)      5/49 (10%)      7/50 (14%)     |
|ADJUSTED (b)           |     35.6%           34.0%           70.3%          |     20.8%           17.2%           21.9%          |
|TERMINAL (d)           |     8/36 (22%)     13/40 (33%)     23/36 (64%)     |     4/22 (18%)      5/29 (17%)      7/32 (22%)     |
|FIRST INCIDENCE (DAYS) |      440             647             500           |      688             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.003 **      P=0.326N        P=0.007 **     |     P=0.564         P=0.466N        P=0.613N       |
|INCIDENTAL TUMOR       |     P=0.001 **      P=0.564N        P=0.002 **     |     P=0.504         P=0.537N        P=0.570        |
|LOGISTIC REGRESSION    |     P=0.001 **      P=0.421N        P=0.002 **     |     P=0.441         P=0.599N        P=0.502        |
|COCHRAN-ARMITAGE       |     P=0.002 **                                     |     P=0.319                                        |
|FISHER EXACT           |                     P=0.414N        P=0.002 **     |                     P=0.617         P=0.380        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   4
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)      6/14 (43%)      4/50 (8%)      |     3/50 (6%)       2/21 (10%)      3/50 (6%)      |
|ADJUSTED (b)           |     16.7%           63.3%           11.1%          |     11.4%           33.3%            8.4%          |
|TERMINAL (d)           |     6/36 (17%)      5/8 (63%)       4/36 (11%)     |     2/22 (9%)       2/6 (33%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         612             730 (T)       |      631             731 (T)         568           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.333N        P=0.008 **      P=0.368N       |     P=0.450N        P=0.421         P=0.578N       |
|INCIDENTAL TUMOR       |     P=0.349N        P=0.005 **      P=0.368N       |     P=0.508         P=0.395         P=0.474        |
|LOGISTIC REGRESSION    |     P=0.348N        P=0.003 **      P=0.368N       |     P=0.552         P=0.228         P=0.641        |
|COCHRAN-ARMITAGE       |     P=0.334N                                       |     P=0.580                                        |
|FISHER EXACT           |                     P=0.017 *       P=0.370N       |                     P=0.466         P=0.661N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)      6/14 (43%)      5/50 (10%)     |     3/50 (6%)       3/21 (14%)      3/50 (6%)      |
|ADJUSTED (b)           |     16.7%           63.3%           13.9%          |     11.4%           35.0%            8.4%          |
|TERMINAL (d)           |     6/36 (17%)      5/8 (63%)       5/36 (14%)     |     2/22 (9%)       2/6 (33%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         612             730 (T)       |      631             569             568           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.446N        P=0.008 **      P=0.500N       |     P=0.464N        P=0.243         P=0.578N       |
|INCIDENTAL TUMOR       |     P=0.462N        P=0.005 **      P=0.500N       |     P=0.445         P=0.206         P=0.474        |
|LOGISTIC REGRESSION    |     P=0.460N        P=0.003 **      P=0.500N       |     P=0.541         P=0.094         P=0.641        |
|COCHRAN-ARMITAGE       |     P=0.446N                                       |     P=0.575                                        |
|FISHER EXACT           |                     P=0.017 *       P=0.500N       |                     P=0.241         P=0.661N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   5
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/47 (2%)       0/5 (0%)        1/45 (2%)      |     8/44 (18%)      5/17 (29%)      3/47 (6%)      |
|ADJUSTED (b)           |      2.6%            0.0%            3.0%          |     35.1%           76.5%            9.4%          |
|TERMINAL (d)           |     0/35 (0%)       0/0             1/33 (3%)      |     7/21 (33%)      3/4 (75%)       3/32 (9%)      |
|FIRST INCIDENCE (DAYS) |      712             ---             730 (T)       |      652             624             731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.641         P=0.490N        P=0.751        |     P=0.018N*       P=0.126         P=0.021N*      |
|INCIDENTAL TUMOR       |     P=0.631           (e)           P=0.754        |     P=0.042N*       P=0.016 *       P=0.028N*      |
|LOGISTIC REGRESSION    |     P=0.626         P=0.995N        P=0.750        |     P=0.059N        P=0.012 *       P=0.053N       |
|COCHRAN-ARMITAGE       |     P=0.632                                        |     P=0.073N                                       |
|FISHER EXACT           |                     P=0.904N        P=0.742        |                     P=0.265         P=0.080N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/47 (2%)       0/5 (0%)        1/45 (2%)      |     8/44 (18%)      5/17 (29%)      4/47 (9%)      |
|ADJUSTED (b)           |      2.6%            0.0%            3.0%          |     35.1%           76.5%           11.7%          |
|TERMINAL (d)           |     0/35 (0%)       0/0             1/33 (3%)      |     7/21 (33%)      3/4 (75%)       3/32 (9%)      |
|FIRST INCIDENCE (DAYS) |      712             ---             730 (T)       |      652             624             605           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.641         P=0.490N        P=0.751        |     P=0.040N*       P=0.126         P=0.056N       |
|INCIDENTAL TUMOR       |     P=0.631           (e)           P=0.754        |     P=0.101N        P=0.016 *       P=0.096N       |
|LOGISTIC REGRESSION    |     P=0.626         P=0.995N        P=0.750        |     P=0.125N        P=0.012 *       P=0.143N       |
|COCHRAN-ARMITAGE       |     P=0.632                                        |     P=0.127N                                       |
|FISHER EXACT           |                     P=0.904N        P=0.742        |                     P=0.265         P=0.146N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   6
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.8%            2.5%            5.6%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/36 (3%)       1/40 (3%)       2/36 (6%)      |     0/22 (0%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         730 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.377         P=0.738N        P=0.500        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.377         P=0.738N        P=0.500        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.377         P=0.738N        P=0.500        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.379                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.753N        P=0.500        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       2/50 (4%)       7/50 (14%)     |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      6.8%            4.5%           16.8%          |      0.0%            2.6%            2.4%          |
|TERMINAL (d)           |     0/36 (0%)       1/40 (3%)       3/36 (8%)      |     0/22 (0%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      593             612             618           |      ---             606             494           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.101         P=0.475N        P=0.164        |     P=0.303         P=0.475         P=0.465        |
|INCIDENTAL TUMOR       |     P=0.052         P=0.672         P=0.085        |     P=0.325         P=0.419         P=0.846        |
|LOGISTIC REGRESSION    |     P=0.058         P=0.465N        P=0.095        |     P=0.388         P=0.542         P=0.618        |
|COCHRAN-ARMITAGE       |     P=0.099                                        |     P=0.332                                        |
|FISHER EXACT           |                     P=0.500N        P=0.159        |                     P=0.500         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   7
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       3/50 (6%)       9/50 (18%)     |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      9.4%            7.0%           21.1%          |      5.4%            2.6%            2.4%          |
|TERMINAL (d)           |     1/36 (3%)       2/40 (5%)       4/36 (11%)     |     0/22 (0%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      593             612             598           |      652             606             494           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.077         P=0.462N        P=0.127        |     P=0.407N        P=0.544N        P=0.523N       |
|INCIDENTAL TUMOR       |     P=0.035 *       P=0.659         P=0.055        |     P=0.564N        P=0.698         P=0.582N       |
|LOGISTIC REGRESSION    |     P=0.040 *       P=0.482N        P=0.061        |     P=0.331N        P=0.472N        P=0.440N       |
|COCHRAN-ARMITAGE       |     P=0.073                                        |     P=0.378N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.117        |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       2/50 (4%)       8/50 (16%)     |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      6.8%            4.5%           18.6%          |      5.4%            2.6%            2.4%          |
|TERMINAL (d)           |     0/36 (0%)       1/40 (3%)       3/36 (8%)      |     0/22 (0%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      593             612             598           |      652             606             494           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.058         P=0.475N        P=0.109        |     P=0.407N        P=0.544N        P=0.523N       |
|INCIDENTAL TUMOR       |     P=0.022 *       P=0.672         P=0.040 *      |     P=0.564N        P=0.698         P=0.582N       |
|LOGISTIC REGRESSION    |     P=0.024 *       P=0.465N        P=0.044 *      |     P=0.331N        P=0.472N        P=0.440N       |
|COCHRAN-ARMITAGE       |     P=0.055                                        |     P=0.378N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.100        |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   8
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            2.2%          |      5.4%            0.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       0/40 (0%)       0/36 (0%)      |     0/22 (0%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             598           |      652             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.270           (e)           P=0.500        |     P=0.103N        P=0.269N        P=0.243N       |
|INCIDENTAL TUMOR       |     P=0.225           (e)           P=0.419        |     P=0.264N        P=0.500N        P=0.500N       |
|LOGISTIC REGRESSION    |     P=0.267           (e)           P=0.562        |     P=0.094N        P=0.228N        P=0.231N       |
|COCHRAN-ARMITAGE       |     P=0.270                                        |     P=0.095N                                       |
|FISHER EXACT           |                       (e)           P=0.500        |                     P=0.247N        P=0.247N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            2.8%          |      9.1%            0.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       0/40 (0%)       1/36 (3%)      |     2/22 (9%)       0/29 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             730 (T)       |      731 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.267           (e)           P=0.500        |     P=0.060N        P=0.179N        P=0.160N       |
|INCIDENTAL TUMOR       |     P=0.267           (e)           P=0.500        |     P=0.060N        P=0.179N        P=0.160N       |
|LOGISTIC REGRESSION    |     P=0.267           (e)           P=0.500        |     P=0.060N        P=0.179N        P=0.160N       |
|COCHRAN-ARMITAGE       |     P=0.270                                        |     P=0.095N                                       |
|FISHER EXACT           |                       (e)           P=0.500        |                     P=0.247N        P=0.247N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE   9
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |     5/50 (10%)      0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      2.8%            0.0%            2.8%          |     18.8%            0.0%            6.3%          |
|TERMINAL (d)           |     1/36 (3%)       0/40 (0%)       1/36 (3%)      |     3/22 (14%)      0/29 (0%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         ---             730 (T)       |      669             ---             731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.671N        P=0.479N        P=0.762        |     P=0.065N        P=0.023N*       P=0.118N       |
|INCIDENTAL TUMOR       |     P=0.671N        P=0.479N        P=0.762        |     P=0.132N        P=0.049N*       P=0.214N       |
|LOGISTIC REGRESSION    |     P=0.671N        P=0.479N        P=0.762        |     P=0.114N        P=0.038N*       P=0.206N       |
|COCHRAN-ARMITAGE       |     P=0.668N                                       |     P=0.117N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.753N       |                     P=0.028N*       P=0.218N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |     3/50 (6%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      2.8%            0.0%            0.0%          |     10.2%            0.0%            6.3%          |
|TERMINAL (d)           |     1/36 (3%)       0/40 (0%)       0/36 (0%)      |     1/22 (5%)       0/29 (0%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         ---             ---           |      669             ---             731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.267N        P=0.479N        P=0.500N       |     P=0.303N        P=0.111N        P=0.384N       |
|INCIDENTAL TUMOR       |     P=0.267N        P=0.479N        P=0.500N       |     P=0.485N        P=0.232N        P=0.586N       |
|LOGISTIC REGRESSION    |     P=0.267N        P=0.479N        P=0.500N       |     P=0.399N        P=0.134N        P=0.512N       |
|COCHRAN-ARMITAGE       |     P=0.270N                                       |     P=0.390N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.121N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE  10
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/48 (0%)       0/5 (0%)        1/49 (2%)      |     2/48 (4%)       0/14 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            2.9%          |      7.3%            0.0%            0.0%          |
|TERMINAL (d)           |     0/35 (0%)       0/0             1/35 (3%)      |     1/22 (5%)       0/0             0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             730 (T)       |      663             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.309           (e)           P=0.500        |     P=0.094N        P=0.518N        P=0.196N       |
|INCIDENTAL TUMOR       |     P=0.309           (e)           P=0.500        |     P=0.180N          (e)           P=0.295N       |
|LOGISTIC REGRESSION    |     P=0.309           (e)           P=0.500        |     P=0.137N        P=0.881N        P=0.243N       |
|COCHRAN-ARMITAGE       |     P=0.307                                        |     P=0.121N                                       |
|FISHER EXACT           |                       (e)           P=0.505        |                     P=0.597N        P=0.237N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |                                                    |      0.0%            6.9%            0.0%          |
|TERMINAL (d)           |                                                    |     0/22 (0%)       2/29 (7%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      ---             731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.593N        P=0.300           (e)          |
|INCIDENTAL TUMOR       |                                                    |     P=0.593N        P=0.300           (e)          |
|LOGISTIC REGRESSION    |                                                    |     P=0.593N        P=0.300           (e)          |
|COCHRAN-ARMITAGE       |                                                    |     P=0.668                                        |
|FISHER EXACT           |                                                    |                     P=0.247           (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE  11
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            7.0%            0.0%          |      0.0%            3.4%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       2/40 (5%)       0/36 (0%)      |     0/22 (0%)       1/29 (3%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             627             ---           |      ---             731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.636         P=0.138           (e)          |     P=0.684N        P=0.555           (e)          |
|INCIDENTAL TUMOR       |     P=0.595         P=0.094           (e)          |     P=0.684N        P=0.555           (e)          |
|LOGISTIC REGRESSION    |     P=0.639         P=0.120           (e)          |     P=0.685N        P=0.555           (e)          |
|COCHRAN-ARMITAGE       |     P=0.638                                        |     P=0.730                                        |
|FISHER EXACT           |                     P=0.121           (e)          |                     P=0.500           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       0/50 (0%)      |     1/50 (2%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            7.0%            0.0%          |      2.1%            3.4%            3.1%          |
|TERMINAL (d)           |     0/36 (0%)       2/40 (5%)       0/36 (0%)      |     0/22 (0%)       1/29 (3%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             627             ---           |      572             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.636         P=0.138           (e)          |     P=0.594N        P=0.754N        P=0.744N       |
|INCIDENTAL TUMOR       |     P=0.595         P=0.094           (e)          |     P=0.604         P=0.749         P=0.678        |
|LOGISTIC REGRESSION    |     P=0.639         P=0.120           (e)          |     P=0.627         P=0.761N        P=0.763N       |
|COCHRAN-ARMITAGE       |     P=0.638                                        |     P=0.640                                        |
|FISHER EXACT           |                     P=0.121           (e)          |                     P=0.753N        P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE  12
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)      8/50 (16%)      1/50 (2%)      |    11/50 (22%)      8/50 (16%)      8/50 (16%)     |
|ADJUSTED (b)           |     17.5%           18.2%            2.8%          |     34.3%           25.0%           22.8%          |
|TERMINAL (d)           |     5/36 (14%)      5/40 (13%)      1/36 (3%)      |     5/22 (23%)      6/29 (21%)      6/32 (19%)     |
|FIRST INCIDENCE (DAYS) |      558             612             730 (T)       |      599             612             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.040N*       P=0.565         P=0.036N*      |     P=0.129N        P=0.226N        P=0.163N       |
|INCIDENTAL TUMOR       |     P=0.057N        P=0.410         P=0.044N*      |     P=0.344N        P=0.365N        P=0.407N       |
|LOGISTIC REGRESSION    |     P=0.038N*       P=0.501         P=0.031N*      |     P=0.305N        P=0.368N        P=0.352N       |
|COCHRAN-ARMITAGE       |     P=0.038N*                                      |     P=0.257N                                       |
|FISHER EXACT           |                     P=0.500         P=0.030N*      |                     P=0.306N        P=0.306N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)      8/50 (16%)      1/50 (2%)      |    11/50 (22%)      8/50 (16%)      8/50 (16%)     |
|ADJUSTED (b)           |     17.5%           18.2%            2.8%          |     34.3%           25.0%           22.8%          |
|TERMINAL (d)           |     5/36 (14%)      5/40 (13%)      1/36 (3%)      |     5/22 (23%)      6/29 (21%)      6/32 (19%)     |
|FIRST INCIDENCE (DAYS) |      558             612             730 (T)       |      599             612             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.040N*       P=0.565         P=0.036N*      |     P=0.129N        P=0.226N        P=0.163N       |
|INCIDENTAL TUMOR       |     P=0.057N        P=0.410         P=0.044N*      |     P=0.344N        P=0.365N        P=0.407N       |
|LOGISTIC REGRESSION    |     P=0.038N*       P=0.501         P=0.031N*      |     P=0.305N        P=0.368N        P=0.352N       |
|COCHRAN-ARMITAGE       |     P=0.038N*                                      |     P=0.257N                                       |
|FISHER EXACT           |                     P=0.500         P=0.030N*      |                     P=0.306N        P=0.306N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE  13
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    17/50 (34%)     17/50 (34%)     30/50 (60%)     |    20/50 (40%)     13/50 (26%)     15/50 (30%)     |
|ADJUSTED (b)           |     42.2%           40.2%           76.7%          |     64.0%           40.0%           42.4%          |
|TERMINAL (d)           |    13/36 (36%)     15/40 (38%)     27/36 (75%)     |    12/22 (55%)     10/29 (34%)     12/32 (38%)     |
|FIRST INCIDENCE (DAYS) |      627             612             500           |      572             569             568           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.005 **      P=0.450N        P=0.008 **     |     P=0.034N*       P=0.037N*       P=0.041N*      |
|INCIDENTAL TUMOR       |     P=0.005 **      P=0.572N        P=0.006 **     |     P=0.241N        P=0.142N        P=0.278N       |
|LOGISTIC REGRESSION    |     P=0.004 **      P=0.567N        P=0.005 **     |     P=0.205N        P=0.155N        P=0.253N       |
|COCHRAN-ARMITAGE       |     P=0.006 **                                     |     P=0.167N                                       |
|FISHER EXACT           |                     P=0.583N        P=0.008 **     |                     P=0.101N        P=0.201N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    18/50 (36%)     17/50 (34%)     21/50 (42%)     |    17/50 (34%)     12/50 (24%)     12/50 (24%)     |
|ADJUSTED (b)           |     37.6%           38.3%           44.7%          |     49.9%           33.4%           30.9%          |
|TERMINAL (d)           |     7/36 (19%)     13/40 (33%)     10/36 (28%)     |     8/22 (36%)      7/29 (24%)      7/32 (22%)     |
|FIRST INCIDENCE (DAYS) |      440             612             500           |      596             431             376           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.316         P=0.409N        P=0.352        |     P=0.082N        P=0.147N        P=0.096N       |
|INCIDENTAL TUMOR       |     P=0.199         P=0.372         P=0.201        |     P=0.231N        P=0.255N        P=0.247N       |
|LOGISTIC REGRESSION    |     P=0.229         P=0.486N        P=0.249        |     P=0.178N        P=0.219N        P=0.203N       |
|COCHRAN-ARMITAGE       |     P=0.303                                        |     P=0.156N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.341        |                     P=0.189N        P=0.189N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05063 TEST: 02                                                 PAGE  14
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PHENYLBUTAZONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         0.15G/KG        0.3 G/KG      |      VEHICLE         0.15G/KG        0.3 G/KG      |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    30/50 (60%)     28/50 (56%)     40/50 (80%)     |    31/50 (62%)     20/50 (40%)     25/50 (50%)     |
|ADJUSTED (b)           |     62.3%           62.0%           85.1%          |     84.5%           56.1%           63.4%          |
|TERMINAL (d)           |    18/36 (50%)     23/40 (58%)     29/36 (81%)     |    17/22 (77%)     14/29 (48%)     18/32 (56%)     |
|FIRST INCIDENCE (DAYS) |      440             612             500           |      572             431             376           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.051         P=0.285N        P=0.070        |     P=0.024N*       P=0.010N**      P=0.026N*      |
|INCIDENTAL TUMOR       |     P=0.010 **      P=0.527         P=0.009 **     |     P=0.183N        P=0.031N*       P=0.199N       |
|LOGISTIC REGRESSION    |     P=0.012 *       P=0.437N        P=0.012 *      |     P=0.221N        P=0.051N        P=0.254N       |
|COCHRAN-ARMITAGE       |     P=0.023 *                                      |     P=0.135N                                       |
|FISHER EXACT           |                     P=0.420N        P=0.024 *      |                     P=0.022N*       P=0.157N       |
|=================================================================================================================================|
 
 (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).