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TR 395 Mouse Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                                     PROBENECID                                      DATE: 09/04/94       
EXPERIMENT: 05030 TEST: 02                                                                                     TIME: 15:19:31       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 56097        
PATHOLOGIST: K. MURTHY                       S. EUSTIS                                                         CAS: 000057669       
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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                                                     PROBENECID                                      DATE: 09/04/94      
EXPERIMENT: 05030 TEST: 02                                                                                     TIME: 15:19:31      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 56097       
PATHOLOGIST: K. MURTHY                       S. EUSTIS                                                         CAS: 000057669      
 
 
 
 
 
                                                    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                                                     PROBENECID                                      DATE: 09/04/94       
EXPERIMENT: 05030 TEST: 02                                                                                     TIME: 15:19:31       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 56097        
PATHOLOGIST: K. MURTHY                       S. EUSTIS                                                         CAS: 000057669       
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                           IN THE ANALYSIS OF THE STUDY OF PROBENECID
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                             Skin: Subcutaneous Tissue     Fibroma
                                                           Neurofibroma or Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, or Sarcoma
                             All Organs                    Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE 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
                             All Organs                    Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   1
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |     0/49 (0%)       0/49 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      5.3%            4.0%            0.0%          |      0.0%            0.0%            3.1%          |
|TERMINAL (d)           |     2/38 (5%)       0/23 (0%)       0/24 (0%)      |     0/32 (0%)       0/32 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      731 (T)         717             ---           |      ---             ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.268N        P=0.662N        P=0.344N       |     P=0.312           (e)           P=0.500        |
|INCIDENTAL TUMOR       |     P=0.204N        P=0.463N        P=0.344N       |     P=0.312           (e)           P=0.500        |
|LOGISTIC REGRESSION    |     P=0.241N        P=0.627N        P=0.344N       |     P=0.312           (e)           P=0.500        |
|COCHRAN-ARMITAGE       |     P=0.195N                                       |     P=0.315                                        |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                       (e)           P=0.505        |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |     0/49 (0%)       1/49 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.3%            0.0%            0.0%          |      0.0%            2.9%            0.0%          |
|TERMINAL (d)           |     2/38 (5%)       0/23 (0%)       0/24 (0%)      |     0/32 (0%)       0/32 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      731 (T)         ---             ---           |      ---             694             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.291N        P=0.354N        P=0.344N       |     P=0.698N        P=0.483           (e)          |
|INCIDENTAL TUMOR       |     P=0.291N        P=0.354N        P=0.344N       |     P=0.843         P=0.362           (e)          |
|LOGISTIC REGRESSION    |     P=0.291N        P=0.354N        P=0.344N       |     P=0.695N        P=0.494           (e)          |
|COCHRAN-ARMITAGE       |     P=0.221N                                       |     P=0.685N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.247N       |                     P=0.500           (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   2
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       1/50 (2%)       0/50 (0%)      |     0/49 (0%)       1/49 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |     10.5%            4.0%            0.0%          |      0.0%            2.9%            3.1%          |
|TERMINAL (d)           |     4/38 (11%)      0/23 (0%)       0/24 (0%)      |     0/32 (0%)       0/32 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      731 (T)         717             ---           |      ---             694             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.108N        P=0.352N        P=0.135N       |     P=0.464         P=0.483         P=0.500        |
|INCIDENTAL TUMOR       |     P=0.080N        P=0.209N        P=0.135N       |     P=0.345         P=0.362         P=0.500        |
|LOGISTIC REGRESSION    |     P=0.089N        P=0.309N        P=0.135N       |     P=0.453         P=0.494         P=0.500        |
|COCHRAN-ARMITAGE       |     P=0.059N                                       |     P=0.477                                        |
|FISHER EXACT           |                     P=0.181N        P=0.059N       |                     P=0.500         P=0.505        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       1/50 (2%)      |     0/48 (0%)       0/49 (0%)       1/49 (2%)      |
|ADJUSTED (b)           |      0.0%           11.0%            2.9%          |      0.0%            0.0%            3.1%          |
|TERMINAL (d)           |     0/38 (0%)       1/23 (4%)       0/24 (0%)      |     0/32 (0%)       0/32 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             645             634           |      ---             ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.559         P=0.066         P=0.468        |     P=0.312           (e)           P=0.500        |
|INCIDENTAL TUMOR       |     P=0.556N        P=0.246         P=0.682        |     P=0.312           (e)           P=0.500        |
|LOGISTIC REGRESSION    |     P=0.618         P=0.084         P=0.506        |     P=0.312           (e)           P=0.500        |
|COCHRAN-ARMITAGE       |     P=0.636                                        |     P=0.314                                        |
|FISHER EXACT           |                     P=0.121         P=0.500        |                       (e)           P=0.505        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   3
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    12/50 (24%)      2/50 (4%)      10/50 (20%)     |     3/48 (6%)       2/49 (4%)      14/49 (29%)     |
|ADJUSTED (b)           |     27.6%            7.6%           33.4%          |      7.6%            5.5%           41.0%          |
|TERMINAL (d)           |     7/38 (18%)      0/23 (0%)       6/24 (25%)     |     1/32 (3%)       1/32 (3%)      12/32 (38%)     |
|FIRST INCIDENCE (DAYS) |      541             659             515           |      612             595             586           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.268         P=0.041N*       P=0.442        |     P<0.001 **      P=0.535N        P=0.003 **     |
|INCIDENTAL TUMOR       |     P=0.579N        P=0.002N**      P=0.369N       |     P<0.001 **      P=0.500N        P=0.001 **     |
|LOGISTIC REGRESSION    |     P=0.427         P=0.008N**      P=0.470N       |     P<0.001 **      P=0.447N        P=0.002 **     |
|COCHRAN-ARMITAGE       |     P=0.474                                        |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.004N**      P=0.405N       |                     P=0.490N        P=0.004 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)     12/50 (24%)     11/50 (22%)     |     2/48 (4%)       2/49 (4%)       3/49 (6%)      |
|ADJUSTED (b)           |     16.3%           36.8%           29.3%          |      5.3%            5.5%            9.0%          |
|TERMINAL (d)           |     3/38 (8%)       4/23 (17%)      2/24 (8%)      |     0/32 (0%)       1/32 (3%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      522             492             438           |      687             595             716           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.175         P=0.038 *       P=0.109        |     P=0.405         P=0.661         P=0.483        |
|INCIDENTAL TUMOR       |     P=0.546N        P=0.425         P=0.564        |     P=0.224         P=0.604         P=0.202        |
|LOGISTIC REGRESSION    |     P=0.569         P=0.164         P=0.469        |     P=0.395         P=0.683N        P=0.146        |
|COCHRAN-ARMITAGE       |     P=0.294                                        |     P=0.432                                        |
|FISHER EXACT           |                     P=0.154         P=0.218        |                     P=0.684N        P=0.510        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   4
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/50 (30%)     12/50 (24%)     19/50 (38%)     |     5/48 (10%)      3/49 (6%)      16/49 (33%)     |
|ADJUSTED (b)           |     33.8%           36.8%           50.1%          |     12.5%            8.5%           45.6%          |
|TERMINAL (d)           |     9/38 (24%)      4/23 (17%)      7/24 (29%)     |     1/32 (3%)       2/32 (6%)      13/32 (41%)     |
|FIRST INCIDENCE (DAYS) |      522             492             438           |      612             595             586           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.058         P=0.404         P=0.070        |     P<0.001 **      P=0.402N        P=0.007 **     |
|INCIDENTAL TUMOR       |     P=0.352         P=0.185N        P=0.490        |     P<0.001 **      P=0.450N        P<0.001 **     |
|LOGISTIC REGRESSION    |     P=0.323         P=0.283N        P=0.474        |     P<0.001 **      P=0.329N        P<0.001 **     |
|COCHRAN-ARMITAGE       |     P=0.153                                        |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.326N        P=0.263        |                     P=0.346N        P=0.007 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/50 (30%)     12/50 (24%)     19/50 (38%)     |     5/48 (10%)      3/49 (6%)      16/49 (33%)     |
|ADJUSTED (b)           |     33.8%           36.8%           50.1%          |     12.5%            8.5%           45.6%          |
|TERMINAL (d)           |     9/38 (24%)      4/23 (17%)      7/24 (29%)     |     1/32 (3%)       2/32 (6%)      13/32 (41%)     |
|FIRST INCIDENCE (DAYS) |      522             492             438           |      612             595             586           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.058         P=0.404         P=0.070        |     P<0.001 **      P=0.402N        P=0.007 **     |
|INCIDENTAL TUMOR       |     P=0.352         P=0.185N        P=0.490        |     P<0.001 **      P=0.450N        P<0.001 **     |
|LOGISTIC REGRESSION    |     P=0.323         P=0.283N        P=0.474        |     P<0.001 **      P=0.329N        P<0.001 **     |
|COCHRAN-ARMITAGE       |     P=0.153                                        |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.326N        P=0.263        |                     P=0.346N        P=0.007 **     |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   5
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/49 (6%)       4/50 (8%)       4/50 (8%)      |     1/49 (2%)       4/23 (17%)      5/49 (10%)     |
|ADJUSTED (b)           |      7.9%           15.1%           12.9%          |      3.0%           35.0%           15.1%          |
|TERMINAL (d)           |     3/38 (8%)       2/23 (9%)       1/24 (4%)      |     0/32 (0%)       3/9 (33%)       4/32 (13%)     |
|FIRST INCIDENCE (DAYS) |      731 (T)         645             620           |      722             595             716           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.332         P=0.269         P=0.319        |     P=0.212         P=0.029 *       P=0.105        |
|INCIDENTAL TUMOR       |     P=0.607         P=0.507         P=0.621        |     P=0.143         P=0.015 *       P=0.036 *      |
|LOGISTIC REGRESSION    |     P=0.441         P=0.347         P=0.444        |     P=0.189         P=0.008 **      P=0.081        |
|COCHRAN-ARMITAGE       |     P=0.497                                        |     P=0.215                                        |
|FISHER EXACT           |                     P=0.511         P=0.511        |                     P=0.033 *       P=0.102        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       0/50 (0%)       2/50 (4%)      |     2/49 (4%)       0/23 (0%)       1/49 (2%)      |
|ADJUSTED (b)           |      5.1%            0.0%            6.5%          |      6.0%            0.0%            3.1%          |
|TERMINAL (d)           |     1/38 (3%)       0/23 (0%)       1/24 (4%)      |     1/32 (3%)       0/9 (0%)        1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      680             ---             568           |      721             ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.436         P=0.342N        P=0.572        |     P=0.514N        P=0.376N        P=0.507N       |
|INCIDENTAL TUMOR       |     P=0.623         P=0.131N        P=0.578N       |     P=0.604N        P=0.534N        P=0.629N       |
|LOGISTIC REGRESSION    |     P=0.508         P=0.285N        P=0.684        |     P=0.510N        P=0.549N        P=0.530N       |
|COCHRAN-ARMITAGE       |     P=0.525                                        |     P=0.509N                                       |
|FISHER EXACT           |                     P=0.242N        P=0.684N       |                     P=0.460N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   6
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/49 (10%)      4/50 (8%)       6/50 (12%)     |     3/49 (6%)       4/23 (17%)      6/49 (12%)     |
|ADJUSTED (b)           |     12.8%           15.1%           18.7%          |      8.8%           35.0%           18.1%          |
|TERMINAL (d)           |     4/38 (11%)      2/23 (9%)       2/24 (8%)      |     1/32 (3%)       3/9 (33%)       5/32 (16%)     |
|FIRST INCIDENCE (DAYS) |      680             645             568           |      721             595             716           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.244         P=0.502         P=0.281        |     P=0.311         P=0.159         P=0.242        |
|INCIDENTAL TUMOR       |     P=0.565         P=0.433N        P=0.587N       |     P=0.200         P=0.071         P=0.090        |
|LOGISTIC REGRESSION    |     P=0.362         P=0.616         P=0.447        |     P=0.281         P=0.048 *       P=0.195        |
|COCHRAN-ARMITAGE       |     P=0.416                                        |     P=0.318                                        |
|FISHER EXACT           |                     P=0.487N        P=0.514        |                     P=0.141         P=0.243        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/38 (0%)       0/44 (0%)       0/44 (0%)      |     2/41 (5%)       0/13 (0%)       4/38 (11%)     |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      6.5%            0.0%           13.8%          |
|TERMINAL (d)           |     0/29 (0%)       0/22 (0%)       0/22 (0%)      |     2/31 (6%)       0/3 (0%)        4/29 (14%)     |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      730 (T)         ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.246         P=0.794N        P=0.304        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.246         P=0.794N        P=0.304        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.246         P=0.794N        P=0.304        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.200                                        |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.573N        P=0.302        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   7
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       3/50 (6%)      |     0/49 (0%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%           11.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/38 (0%)       0/23 (0%)       1/24 (4%)      |     0/32 (0%)       0/32 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             646           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.018 *         (e)           P=0.066        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.035 *         (e)           P=0.224        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.026 *         (e)           P=0.097        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.030 *                                      |       (e)                                          |
|FISHER EXACT           |                       (e)           P=0.121        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       4/50 (8%)       3/50 (6%)      |     0/49 (0%)       0/49 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.1%           13.0%            9.8%          |      0.0%            0.0%            3.0%          |
|TERMINAL (d)           |     0/38 (0%)       2/23 (9%)       1/24 (4%)      |     0/32 (0%)       0/32 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      390             390             515           |      ---             ---             717           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.320         P=0.114         P=0.231        |     P=0.308           (e)           P=0.494        |
|INCIDENTAL TUMOR       |     P=0.287         P=0.251         P=0.357        |     P=0.139           (e)           P=0.261        |
|LOGISTIC REGRESSION    |     P=0.417         P=0.246         P=0.340        |     P=0.297           (e)           P=0.479        |
|COCHRAN-ARMITAGE       |     P=0.402                                        |     P=0.315                                        |
|FISHER EXACT           |                     P=0.181         P=0.309        |                       (e)           P=0.505        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   8
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibroma or Fibroma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       4/50 (8%)      |     0/49 (0%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            3.0%           13.7%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/38 (0%)       0/23 (0%)       1/24 (4%)      |     0/32 (0%)       0/32 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             635             635           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.017 *       P=0.462         P=0.032 *      |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.090         P=0.443         P=0.164        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.025 *       P=0.499         P=0.052        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.028 *                                      |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.059        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       7/50 (14%)      6/50 (12%)     |     0/49 (0%)       1/49 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.1%           22.0%           18.7%          |      0.0%            3.0%            3.0%          |
|TERMINAL (d)           |     0/38 (0%)       3/23 (13%)      1/24 (4%)      |     0/32 (0%)       0/32 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      390             390             515           |      ---             717             717           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.100         P=0.014 *       P=0.031 *      |     P=0.467         P=0.494         P=0.494        |
|INCIDENTAL TUMOR       |     P=0.228         P=0.028 *       P=0.171        |     P=0.206         P=0.362         P=0.261        |
|LOGISTIC REGRESSION    |     P=0.158         P=0.043 *       P=0.064        |     P=0.451         P=0.484         P=0.479        |
|COCHRAN-ARMITAGE       |     P=0.154                                        |     P=0.477                                        |
|FISHER EXACT           |                     P=0.030 *       P=0.056        |                     P=0.500         P=0.505        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE   9
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       6/50 (12%)      3/50 (6%)      |     0/49 (0%)       1/49 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.1%           19.6%            9.8%          |      0.0%            3.0%            3.0%          |
|TERMINAL (d)           |     0/38 (0%)       3/23 (13%)      1/24 (4%)      |     0/32 (0%)       0/32 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      390             390             515           |      ---             717             717           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.412         P=0.027 *       P=0.231        |     P=0.467         P=0.494         P=0.494        |
|INCIDENTAL TUMOR       |     P=0.464         P=0.061         P=0.357        |     P=0.206         P=0.362         P=0.261        |
|LOGISTIC REGRESSION    |     P=0.527         P=0.078         P=0.340        |     P=0.451         P=0.484         P=0.479        |
|COCHRAN-ARMITAGE       |     P=0.513                                        |     P=0.477                                        |
|FISHER EXACT           |                     P=0.056         P=0.309        |                     P=0.500         P=0.505        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |     3/49 (6%)       3/49 (6%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            4.3%            0.0%          |      9.4%            9.4%            6.3%          |
|TERMINAL (d)           |     0/38 (0%)       1/23 (4%)       0/24 (0%)      |     3/32 (9%)       3/32 (9%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      ---             731 (T)         ---           |      730 (T)         730 (T)         730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.743N        P=0.400           (e)          |     P=0.429N        P=0.665         P=0.500N       |
|INCIDENTAL TUMOR       |     P=0.743N        P=0.400           (e)          |     P=0.429N        P=0.665         P=0.500N       |
|LOGISTIC REGRESSION    |     P=0.743N        P=0.400           (e)          |     P=0.429N        P=0.665         P=0.500N       |
|COCHRAN-ARMITAGE       |     P=0.689N                                       |     P=0.419N                                       |
|FISHER EXACT           |                     P=0.500           (e)          |                     P=0.661N        P=0.490N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE  10
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |     3/49 (6%)       2/49 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            4.3%            0.0%          |      9.4%            6.3%            6.3%          |
|TERMINAL (d)           |     0/38 (0%)       1/23 (4%)       0/24 (0%)      |     3/32 (9%)       2/32 (6%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      ---             731 (T)         ---           |      730 (T)         730 (T)         730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.743N        P=0.400           (e)          |     P=0.485N        P=0.500N        P=0.500N       |
|INCIDENTAL TUMOR       |     P=0.743N        P=0.400           (e)          |     P=0.485N        P=0.500N        P=0.500N       |
|LOGISTIC REGRESSION    |     P=0.743N        P=0.400           (e)          |     P=0.485N        P=0.500N        P=0.500N       |
|COCHRAN-ARMITAGE       |     P=0.689N                                       |     P=0.475N                                       |
|FISHER EXACT           |                     P=0.500           (e)          |                     P=0.500N        P=0.490N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/48 (2%)       0/50 (0%)       0/47 (0%)      |     0/48 (0%)       2/48 (4%)       2/48 (4%)      |
|ADJUSTED (b)           |      2.6%            0.0%            0.0%          |      0.0%            5.9%            6.3%          |
|TERMINAL (d)           |     1/38 (3%)       0/23 (0%)       0/23 (0%)      |     0/32 (0%)       1/32 (3%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      731 (T)         ---             ---           |      ---             686             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.531N        P=0.600N        P=0.600N       |     P=0.285         P=0.228         P=0.238        |
|INCIDENTAL TUMOR       |     P=0.531N        P=0.600N        P=0.600N       |     P=0.216         P=0.166         P=0.238        |
|LOGISTIC REGRESSION    |     P=0.531N        P=0.600N        P=0.600N       |     P=0.259         P=0.223         P=0.238        |
|COCHRAN-ARMITAGE       |     P=0.466N                                       |     P=0.292                                        |
|FISHER EXACT           |                     P=0.490N        P=0.505N       |                     P=0.247         P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE  11
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       2/50 (4%)      |     0/49 (0%)       1/49 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%           11.0%            6.1%          |      0.0%            2.6%            6.3%          |
|TERMINAL (d)           |     0/38 (0%)       1/23 (4%)       0/24 (0%)      |     0/32 (0%)       0/32 (0%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      ---             645             634           |      ---             627             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.302         P=0.066         P=0.195        |     P=0.186         P=0.485         P=0.238        |
|INCIDENTAL TUMOR       |     P=0.567         P=0.246         P=0.495        |     P=0.201         P=0.567         P=0.238        |
|LOGISTIC REGRESSION    |     P=0.362         P=0.084         P=0.240        |     P=0.186         P=0.511         P=0.238        |
|COCHRAN-ARMITAGE       |     P=0.377                                        |     P=0.201                                        |
|FISHER EXACT           |                     P=0.121         P=0.247        |                     P=0.500         P=0.253        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       3/50 (6%)      |     0/49 (0%)       1/49 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%           11.0%           10.0%          |      0.0%            2.6%            6.3%          |
|TERMINAL (d)           |     0/38 (0%)       1/23 (4%)       1/24 (4%)      |     0/32 (0%)       0/32 (0%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      ---             645             634           |      ---             627             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.135         P=0.066         P=0.077        |     P=0.186         P=0.485         P=0.238        |
|INCIDENTAL TUMOR       |     P=0.305         P=0.246         P=0.214        |     P=0.201         P=0.567         P=0.238        |
|LOGISTIC REGRESSION    |     P=0.180         P=0.084         P=0.111        |     P=0.186         P=0.511         P=0.238        |
|COCHRAN-ARMITAGE       |     P=0.195                                        |     P=0.201                                        |
|FISHER EXACT           |                     P=0.121         P=0.121        |                     P=0.500         P=0.253        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE  12
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     0/49 (0%)       2/49 (4%)       3/50 (6%)      |
|ADJUSTED (b)           |      0.0%            2.7%            6.2%          |      0.0%            5.9%            8.6%          |
|TERMINAL (d)           |     0/38 (0%)       0/23 (0%)       1/24 (4%)      |     0/32 (0%)       1/32 (3%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      ---             492             355           |      ---             686             583           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.173         P=0.457         P=0.186        |     P=0.125         P=0.228         P=0.115        |
|INCIDENTAL TUMOR       |     P=0.170         P=0.662         P=0.274        |     P=0.092         P=0.166         P=0.134        |
|LOGISTIC REGRESSION    |     P=0.203         P=0.567         P=0.271        |     P=0.126         P=0.224         P=0.118        |
|COCHRAN-ARMITAGE       |     P=0.195                                        |     P=0.138                                        |
|FISHER EXACT           |                     P=0.500         P=0.247        |                     P=0.247         P=0.125        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       4/50 (8%)       7/50 (14%)     |    11/49 (22%)     11/49 (22%)     10/50 (20%)     |
|ADJUSTED (b)           |      7.9%           14.3%           23.0%          |     28.8%           32.1%           29.0%          |
|TERMINAL (d)           |     3/38 (8%)       2/23 (9%)       4/24 (17%)     |     6/32 (19%)      9/32 (28%)      8/32 (25%)     |
|FIRST INCIDENCE (DAYS) |      731 (T)         492             306           |      612             646             583           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.054         P=0.274         P=0.056        |     P=0.490N        P=0.558         P=0.534N       |
|INCIDENTAL TUMOR       |     P=0.079         P=0.466         P=0.132        |     P=0.445         P=0.418         P=0.448        |
|LOGISTIC REGRESSION    |     P=0.114         P=0.410         P=0.160        |     P=0.555N        P=0.521         P=0.595N       |
|COCHRAN-ARMITAGE       |     P=0.118                                        |     P=0.438N                                       |
|FISHER EXACT           |                     P=0.500         P=0.159        |                     P=0.595N        P=0.479N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE  13
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       3/50 (6%)       5/50 (10%)     |    11/49 (22%)      9/49 (18%)      7/50 (14%)     |
|ADJUSTED (b)           |      7.9%           12.0%           17.3%          |     28.8%           27.0%           21.1%          |
|TERMINAL (d)           |     3/38 (8%)       2/23 (9%)       3/24 (13%)     |     6/32 (19%)      8/32 (25%)      6/32 (19%)     |
|FIRST INCIDENCE (DAYS) |      731 (T)         659             306           |      612             646             716           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.151         P=0.430         P=0.175        |     P=0.229N        P=0.434N        P=0.248N       |
|INCIDENTAL TUMOR       |     P=0.215         P=0.572         P=0.299        |     P=0.385N        P=0.551N        P=0.456N       |
|LOGISTIC REGRESSION    |     P=0.255         P=0.516         P=0.331        |     P=0.272N        P=0.472N        P=0.291N       |
|COCHRAN-ARMITAGE       |     P=0.280                                        |     P=0.194N                                       |
|FISHER EXACT           |                     P=0.661N        P=0.357        |                     P=0.401N        P=0.204N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    18/50 (36%)     10/50 (20%)     19/50 (38%)     |    10/49 (20%)     10/49 (20%)     22/50 (44%)     |
|ADJUSTED (b)           |     41.6%           34.8%           58.2%          |     27.7%           28.9%           62.8%          |
|TERMINAL (d)           |    13/38 (34%)      5/23 (22%)     11/24 (46%)     |     7/32 (22%)      8/32 (25%)     19/32 (59%)     |
|FIRST INCIDENCE (DAYS) |      541             635             515           |      612             595             586           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.062         P=0.407N        P=0.099        |     P=0.002 **      P=0.572         P=0.008 **     |
|INCIDENTAL TUMOR       |     P=0.303         P=0.087N        P=0.494        |     P<0.001 **      P=0.534         P=0.002 **     |
|LOGISTIC REGRESSION    |     P=0.176         P=0.162N        P=0.344        |     P<0.001 **      P=0.532         P=0.002 **     |
|COCHRAN-ARMITAGE       |     P=0.262                                        |     P=0.003 **                                     |
|FISHER EXACT           |                     P=0.059N        P=0.500        |                     P=0.599N        P=0.010 *      |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE  14
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .1G/KG          .4G/KG        |      VEHICLE         .1G/KG          .4G/KG        |
|                       |      MALE            LM              HM            |      FEMALE          LF              HF            |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/50 (30%)     24/50 (48%)     25/50 (50%)     |    15/49 (31%)     16/49 (33%)     17/50 (34%)     |
|ADJUSTED (b)           |     33.8%           65.7%           59.1%          |     38.1%           41.9%           48.4%          |
|TERMINAL (d)           |     9/38 (24%)     11/23 (48%)      8/24 (33%)     |     8/32 (25%)     10/32 (31%)     14/32 (44%)     |
|FIRST INCIDENCE (DAYS) |      390             390             306           |      612             595             583           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.019 *       P=0.003 **      P=0.006 **     |     P=0.368         P=0.454         P=0.386        |
|INCIDENTAL TUMOR       |     P=0.159         P=0.128         P=0.168        |     P=0.111         P=0.256         P=0.119        |
|LOGISTIC REGRESSION    |     P=0.103         P=0.040 *       P=0.077        |     P=0.149         P=0.309         P=0.270        |
|COCHRAN-ARMITAGE       |     P=0.062                                        |     P=0.429                                        |
|FISHER EXACT           |                     P=0.050         P=0.033 *      |                     P=0.500         P=0.442        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    25/50 (50%)     26/50 (52%)     37/50 (74%)     |    23/49 (47%)     21/49 (43%)     31/50 (62%)     |
|ADJUSTED (b)           |     54.2%           67.9%           82.2%          |     55.7%           55.1%           86.0%          |
|TERMINAL (d)           |    17/38 (45%)     11/23 (48%)     16/24 (67%)     |    14/32 (44%)     15/32 (47%)     27/32 (84%)     |
|FIRST INCIDENCE (DAYS) |      390             390             306           |      612             595             583           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.001 **      P=0.053         P<0.001 **     |     P=0.036 *       P=0.481N        P=0.072        |
|INCIDENTAL TUMOR       |     P=0.021 *       P=0.563N        P=0.055        |     P=0.002 **      P=0.500         P=0.005 **     |
|LOGISTIC REGRESSION    |     P=0.006 **      P=0.492         P=0.015 *      |     P=0.002 **      P=0.513         P=0.012 *      |
|COCHRAN-ARMITAGE       |     P=0.006 **                                     |     P=0.047 *                                      |
|FISHER EXACT           |                     P=0.500         P=0.011 *      |                     P=0.420N        P=0.096        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 02                                                 PAGE  15
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROBENECID
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (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).

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