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TR 395 Rat Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                                     PROBENECID                                      DATE: 09/04/94       
EXPERIMENT: 05030 TEST: 01                                                                                     TIME: 13:50:00       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 56097        
PATHOLOGIST: K. MURTHY                       S. EUSTIS                                                         CAS: 57-66-9         
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Mason                                                     PROBENECID                                      DATE: 09/04/94      
EXPERIMENT: 05030 TEST: 01                                                                                     TIME: 13:50:00      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 56097       
PATHOLOGIST: K. MURTHY                       S. EUSTIS                                                         CAS: 57-66-9        
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                                     PROBENECID                                      DATE: 09/04/94       
EXPERIMENT: 05030 TEST: 01                                                                                     TIME: 13:50:00       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 56097        
PATHOLOGIST: K. MURTHY                       S. EUSTIS                                                         CAS: 57-66-9         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                           IN THE ANALYSIS OF THE STUDY OF PROBENECID
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Clitoral/Preputial Gland      Carcinoma
                                                           Carcinoma or Adenoma
                             Islets, Pancreatic            Carcinoma or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                             Testes                        Adenoma
                             Thyroid Gland: C-Cell         Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma or Adenoma
                             Islets, Pancreatic            Adenoma
                                                           Carcinoma or Adenoma
                             Mammary Gland                 Fibroadenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Thyroid Gland: C-Cell         Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Malignant Lymphoma And Histiocytic Sarcoma
                                                           Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,
                                                            NOS, or Undifferentiated Cell Type
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   1
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       0/50 (0%)       0/50 (0%)      |     1/50 (2%)       0/13 (0%)       1/49 (2%)      |
|ADJUSTED (b)           |      5.6%            0.0%            0.0%          |      4.2%            0.0%            3.4%          |
|TERMINAL (d)           |     2/36 (6%)       0/34 (0%)       0/22 (0%)      |     1/24 (4%)       0/3 (0%)        0/18 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         ---             ---           |      729 (T)         ---             649           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.300N        P=0.251N        P=0.352N       |     P=0.598         P=0.892N        P=0.697        |
|INCIDENTAL TUMOR       |     P=0.300N        P=0.251N        P=0.352N       |     P=0.616         P=0.892N        P=0.689        |
|LOGISTIC REGRESSION    |     P=0.300N        P=0.251N        P=0.352N       |     P=0.636         P=0.892N        P=0.718        |
|COCHRAN-ARMITAGE       |     P=0.219N                                       |     P=0.678                                        |
|FISHER EXACT           |                     P=0.242N        P=0.242N       |                     P=0.794N        P=0.747        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    19/49 (39%)     18/50 (36%)      8/50 (16%)     |     2/48 (4%)       1/13 (8%)       1/45 (2%)      |
|ADJUSTED (b)           |     49.9%           45.9%           31.9%          |      6.4%           33.3%            6.3%          |
|TERMINAL (d)           |    17/36 (47%)     13/34 (38%)      6/22 (27%)     |     1/24 (4%)       1/3 (33%)       1/16 (6%)      |
|FIRST INCIDENCE (DAYS) |      707             631             562           |      635             729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.143N        P=0.565         P=0.183N       |     P=0.542N        P=0.628         P=0.628N       |
|INCIDENTAL TUMOR       |     P=0.029N*       P=0.551N        P=0.076N       |     P=0.481N        P=0.609         P=0.553N       |
|LOGISTIC REGRESSION    |     P=0.022N*       P=0.580N        P=0.045N*      |     P=0.497N        P=0.463         P=0.599N       |
|COCHRAN-ARMITAGE       |     P=0.006N**                                     |     P=0.417N                                       |
|FISHER EXACT           |                     P=0.469N        P=0.010N**     |                     P=0.519         P=0.524N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   2
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    20/49 (41%)     19/50 (38%)      8/50 (16%)     |     2/48 (4%)       1/13 (8%)       1/45 (2%)      |
|ADJUSTED (b)           |     52.5%           48.5%           31.9%          |      6.4%           33.3%            6.3%          |
|TERMINAL (d)           |    18/36 (50%)     14/34 (41%)      6/22 (27%)     |     1/24 (4%)       1/3 (33%)       1/16 (6%)      |
|FIRST INCIDENCE (DAYS) |      707             631             562           |      635             729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.106N        P=0.560         P=0.140N       |     P=0.542N        P=0.628         P=0.628N       |
|INCIDENTAL TUMOR       |     P=0.019N*       P=0.555N        P=0.054N       |     P=0.481N        P=0.609         P=0.553N       |
|LOGISTIC REGRESSION    |     P=0.014N*       P=0.585         P=0.030N*      |     P=0.497N        P=0.463         P=0.599N       |
|COCHRAN-ARMITAGE       |     P=0.003N**                                     |     P=0.417N                                       |
|FISHER EXACT           |                     P=0.468N        P=0.006N**     |                     P=0.519         P=0.524N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/49 (12%)      3/15 (20%)      9/50 (18%)     |     3/36 (8%)       7/16 (44%)      1/45 (2%)      |
|ADJUSTED (b)           |     14.1%           34.8%           26.8%          |     10.2%           64.2%            5.3%          |
|TERMINAL (d)           |     3/37 (8%)       2/6 (33%)       3/22 (14%)     |     1/20 (5%)       5/8 (63%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      551             582             491           |      649             593             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.074         P=0.539         P=0.123        |     P=0.148N        P=0.027 *       P=0.368N       |
|INCIDENTAL TUMOR       |     P=0.395         P=0.291         P=0.480        |     P=0.064N        P=0.010 **      P=0.373N       |
|LOGISTIC REGRESSION    |     P=0.334         P=0.401         P=0.373        |     P=0.074N        P=0.003 **      P=0.277N       |
|COCHRAN-ARMITAGE       |     P=0.315                                        |     P=0.048N*                                      |
|FISHER EXACT           |                     P=0.352         P=0.303        |                     P=0.006 **      P=0.229N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   3
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/49 (0%)       2/15 (13%)      1/50 (2%)      |     0/36 (0%)       1/16 (6%)       0/45 (0%)      |
|ADJUSTED (b)           |      0.0%           33.3%            4.3%          |      0.0%           12.5%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       2/6 (33%)       0/22 (0%)      |     0/20 (0%)       1/8 (13%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         727           |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.463         P=0.006 **      P=0.400        |     P=0.650N        P=0.318           (e)          |
|INCIDENTAL TUMOR       |     P=0.627         P=0.006 **      P=0.665        |     P=0.650N        P=0.318           (e)          |
|LOGISTIC REGRESSION    |     P=0.506         P=0.006 **      P=0.429        |     P=0.650N        P=0.318           (e)          |
|COCHRAN-ARMITAGE       |     P=0.640                                        |     P=0.602N                                       |
|FISHER EXACT           |                     P=0.052         P=0.505        |                     P=0.308           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/49 (12%)      5/15 (33%)     10/50 (20%)     |     3/36 (8%)       8/16 (50%)      1/45 (2%)      |
|ADJUSTED (b)           |     14.1%           67.4%           29.9%          |     10.2%           76.1%            5.3%          |
|TERMINAL (d)           |     3/37 (8%)       4/6 (67%)       3/22 (14%)     |     1/20 (5%)       6/8 (75%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      551             582             491           |      649             593             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.056         P=0.111         P=0.074        |     P=0.127N        P=0.009 **      P=0.368N       |
|INCIDENTAL TUMOR       |     P=0.378         P=0.022 *       P=0.409        |     P=0.054N        P=0.003 **      P=0.373N       |
|LOGISTIC REGRESSION    |     P=0.311         P=0.047 *       P=0.269        |     P=0.064N        P<0.001 **      P=0.277N       |
|COCHRAN-ARMITAGE       |     P=0.310                                        |     P=0.038N*                                      |
|FISHER EXACT           |                     P=0.071         P=0.220        |                     P=0.002 **      P=0.229N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   4
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       2/19 (11%)      3/49 (6%)      |     0/50 (0%)       1/11 (9%)       2/50 (4%)      |
|ADJUSTED (b)           |      5.6%           14.9%           10.7%          |      0.0%          100.0%            9.6%          |
|TERMINAL (d)           |     2/36 (6%)       1/8 (13%)       1/22 (5%)      |     0/24 (0%)       1/1 (100%)      1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         699             703           |      ---             729 (T)         705           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.313         P=0.277         P=0.319        |     P=0.207         P=0.009 **      P=0.189        |
|INCIDENTAL TUMOR       |     P=0.574         P=0.206         P=0.501        |     P=0.241         P=0.009 **      P=0.180        |
|LOGISTIC REGRESSION    |     P=0.446         P=0.183         P=0.404        |     P=0.241         P=0.009 **      P=0.184        |
|COCHRAN-ARMITAGE       |     P=0.530                                        |     P=0.292                                        |
|FISHER EXACT           |                     P=0.310         P=0.500        |                     P=0.180         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       3/19 (16%)      3/49 (6%)      |     0/50 (0%)       1/11 (9%)       2/50 (4%)      |
|ADJUSTED (b)           |      5.6%           27.1%           10.7%          |      0.0%          100.0%            9.6%          |
|TERMINAL (d)           |     2/36 (6%)       2/8 (25%)       1/22 (5%)      |     0/24 (0%)       1/1 (100%)      1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         699             703           |      ---             729 (T)         705           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.358         P=0.073         P=0.319        |     P=0.207         P=0.009 **      P=0.189        |
|INCIDENTAL TUMOR       |     P=0.605         P=0.046 *       P=0.501        |     P=0.241         P=0.009 **      P=0.180        |
|LOGISTIC REGRESSION    |     P=0.498         P=0.037 *       P=0.404        |     P=0.241         P=0.009 **      P=0.184        |
|COCHRAN-ARMITAGE       |     P=0.593                                        |     P=0.292                                        |
|FISHER EXACT           |                     P=0.129         P=0.500        |                     P=0.180         P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   5
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            |     1/50 (2%)       1/41 (2%)       0/50 (0%)      |     0/50 (0%)       1/30 (3%)       2/50 (4%)      |
|ADJUSTED (b)           |      2.7%            3.4%            0.0%          |      0.0%            5.9%            9.8%          |
|TERMINAL (d)           |     1/37 (3%)       1/29 (3%)       0/22 (0%)      |     0/24 (0%)       1/17 (6%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         ---           |      ---             729 (T)         721           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.472N        P=0.707         P=0.604N       |     P=0.148         P=0.431         P=0.188        |
|INCIDENTAL TUMOR       |     P=0.472N        P=0.707         P=0.604N       |     P=0.175         P=0.431         P=0.180        |
|LOGISTIC REGRESSION    |     P=0.472N        P=0.707         P=0.604N       |     P=0.162         P=0.431         P=0.181        |
|COCHRAN-ARMITAGE       |     P=0.354N                                       |     P=0.239                                        |
|FISHER EXACT           |                     P=0.701         P=0.500N       |                     P=0.375         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/41 (5%)       0/50 (0%)      |     0/50 (0%)       1/30 (3%)       2/50 (4%)      |
|ADJUSTED (b)           |      2.7%            6.9%            0.0%          |      0.0%            5.9%            9.8%          |
|TERMINAL (d)           |     1/37 (3%)       2/29 (7%)       0/22 (0%)      |     0/24 (0%)       1/17 (6%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         ---           |      ---             729 (T)         721           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.429N        P=0.415         P=0.604N       |     P=0.148         P=0.431         P=0.188        |
|INCIDENTAL TUMOR       |     P=0.429N        P=0.415         P=0.604N       |     P=0.175         P=0.431         P=0.180        |
|LOGISTIC REGRESSION    |     P=0.429N        P=0.415         P=0.604N       |     P=0.162         P=0.431         P=0.181        |
|COCHRAN-ARMITAGE       |     P=0.293N                                       |     P=0.239                                        |
|FISHER EXACT           |                     P=0.425         P=0.500N       |                     P=0.375         P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   6
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/41 (5%)       0/50 (0%)      |     0/50 (0%)       1/30 (3%)       2/50 (4%)      |
|ADJUSTED (b)           |      2.7%            6.9%            0.0%          |      0.0%            5.9%            9.8%          |
|TERMINAL (d)           |     1/37 (3%)       2/29 (7%)       0/22 (0%)      |     0/24 (0%)       1/17 (6%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         ---           |      ---             729 (T)         721           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.429N        P=0.415         P=0.604N       |     P=0.148         P=0.431         P=0.188        |
|INCIDENTAL TUMOR       |     P=0.429N        P=0.415         P=0.604N       |     P=0.175         P=0.431         P=0.180        |
|LOGISTIC REGRESSION    |     P=0.429N        P=0.415         P=0.604N       |     P=0.162         P=0.431         P=0.181        |
|COCHRAN-ARMITAGE       |     P=0.293N                                       |     P=0.239                                        |
|FISHER EXACT           |                     P=0.425         P=0.500N       |                     P=0.375         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       2/18 (11%)      6/50 (12%)     |     2/50 (4%)       2/26 (8%)       1/50 (2%)      |
|ADJUSTED (b)           |      7.7%           16.0%           22.3%          |      8.3%            9.1%            4.2%          |
|TERMINAL (d)           |     2/37 (5%)       1/7 (14%)       4/22 (18%)     |     2/24 (8%)       1/15 (7%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      671             462             580           |      729 (T)         721             695           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.078         P=0.482         P=0.093        |     P=0.490N        P=0.598         P=0.576N       |
|INCIDENTAL TUMOR       |     P=0.205         P=0.535         P=0.180        |     P=0.456N        P=0.401         P=0.593N       |
|LOGISTIC REGRESSION    |     P=0.231         P=0.471         P=0.204        |     P=0.460N        P=0.492         P=0.586N       |
|COCHRAN-ARMITAGE       |     P=0.240                                        |     P=0.357N                                       |
|FISHER EXACT           |                     P=0.399         P=0.243        |                     P=0.423         P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   7
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     3/50 (6%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      9.7%            2.9%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       0/34 (0%)       0/22 (0%)      |     1/24 (4%)       1/35 (3%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      652             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.147N        P=0.214N        P=0.171N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.149N        P=0.380N        P=0.179N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.129N        P=0.295N        P=0.149N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.107N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.309N        P=0.121N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       2/50 (4%)       0/50 (0%)      |    24/50 (48%)     23/50 (46%)      5/50 (10%)     |
|ADJUSTED (b)           |      7.8%            5.3%            0.0%          |     65.7%           48.8%           15.6%          |
|TERMINAL (d)           |     2/37 (5%)       1/34 (3%)       0/22 (0%)      |    12/24 (50%)     11/35 (31%)      1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      708             650             ---           |      593             537             512           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.170N        P=0.539N        P=0.222N       |     P=0.002N**      P=0.149N        P=0.002N**     |
|INCIDENTAL TUMOR       |     P=0.081N        P=0.499N        P=0.125N       |     P<0.001N**      P=0.448         P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.114N        P=0.516N        P=0.165N       |     P<0.001N**      P=0.479N        P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.098N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.500N        P=0.121N       |                     P=0.500N        P<0.001N**     |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   8
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       2/50 (4%)       0/50 (0%)      |    24/50 (48%)     23/50 (46%)      5/50 (10%)     |
|ADJUSTED (b)           |      7.8%            5.3%            0.0%          |     65.7%           48.8%           15.6%          |
|TERMINAL (d)           |     2/37 (5%)       1/34 (3%)       0/22 (0%)      |    12/24 (50%)     11/35 (31%)      1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      708             650             ---           |      593             537             512           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.170N        P=0.539N        P=0.222N       |     P=0.002N**      P=0.149N        P=0.002N**     |
|INCIDENTAL TUMOR       |     P=0.081N        P=0.499N        P=0.125N       |     P<0.001N**      P=0.448         P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.114N        P=0.516N        P=0.165N       |     P<0.001N**      P=0.479N        P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.098N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.500N        P=0.121N       |                     P=0.500N        P<0.001N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Granulosa Cell Tumor Benign                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     2/50 (4%)       1/16 (6%)       1/50 (2%)      |
|ADJUSTED (b)           |                                                    |      7.5%           16.7%            2.7%          |
|TERMINAL (d)           |                                                    |     1/24 (4%)       1/6 (17%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      704             729 (T)         592           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.524N        P=0.738         P=0.578N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.448N        P=0.478         P=0.525N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.459N        P=0.538         P=0.546N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.399N                                       |
|FISHER EXACT           |                                                    |                     P=0.572         P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE   9
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/50 (30%)     14/26 (54%)     17/50 (34%)     |    22/50 (44%)     26/50 (52%)     16/50 (32%)     |
|ADJUSTED (b)           |     35.3%           74.0%           49.9%          |     60.7%           63.2%           60.0%          |
|TERMINAL (d)           |    10/37 (27%)     10/14 (71%)      7/22 (32%)     |    11/24 (46%)     20/35 (57%)      9/19 (47%)     |
|FIRST INCIDENCE (DAYS) |      610             462             513           |      544             592             557           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.083         P=0.045 *       P=0.076        |     P=0.490N        P=0.356N        P=0.466N       |
|INCIDENTAL TUMOR       |     P=0.534N        P=0.018 *       P=0.488        |     P=0.249N        P=0.317         P=0.353N       |
|LOGISTIC REGRESSION    |     P=0.505         P=0.013 *       P=0.352        |     P=0.294N        P=0.339         P=0.385N       |
|COCHRAN-ARMITAGE       |     P=0.540N                                       |     P=0.070N                                       |
|FISHER EXACT           |                     P=0.038 *       P=0.415        |                     P=0.274         P=0.151N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.4%            2.7%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/37 (5%)       0/34 (0%)       0/22 (0%)      |     0/24 (0%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         694             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.275N        P=0.531N        P=0.358N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.192N        P=0.504N        P=0.358N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.228N        P=0.521N        P=0.358N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.195N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  10
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                                             |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      7.0%            2.9%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       0/34 (0%)       0/22 (0%)      |     1/24 (4%)       1/35 (3%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      663             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.251N        P=0.392N        P=0.296N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.250N        P=0.507N        P=0.304N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.236N        P=0.474N        P=0.280N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.195N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.500N        P=0.247N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       1/50 (2%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            5.9%            4.2%          |      4.2%            0.0%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       2/34 (6%)       0/22 (0%)      |     1/24 (4%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             730 (T)         723           |      729 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.423         P=0.220         P=0.408        |     P=0.520N        P=0.425N        P=0.547N       |
|INCIDENTAL TUMOR       |     P=0.563         P=0.220         P=0.665        |     P=0.520N        P=0.425N        P=0.547N       |
|LOGISTIC REGRESSION    |     P=0.467         P=0.220         P=0.447        |     P=0.520N        P=0.425N        P=0.547N       |
|COCHRAN-ARMITAGE       |     P=0.568                                        |     P=0.461N                                       |
|FISHER EXACT           |                     P=0.247         P=0.500        |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  11
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.4%            5.9%            4.5%          |      0.0%            2.9%            0.0%          |
|TERMINAL (d)           |     2/37 (5%)       2/34 (6%)       1/22 (5%)      |     0/24 (0%)       1/35 (3%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         730 (T)       |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.609N        P=0.665         P=0.678N       |     P=0.760N        P=0.575           (e)          |
|INCIDENTAL TUMOR       |     P=0.609N        P=0.665         P=0.678N       |     P=0.760N        P=0.575           (e)          |
|LOGISTIC REGRESSION    |     P=0.609N        P=0.665         P=0.678N       |     P=0.760N        P=0.575           (e)          |
|COCHRAN-ARMITAGE       |     P=0.412N                                       |     P=0.689N                                       |
|FISHER EXACT           |                     P=0.691N        P=0.500N       |                     P=0.500           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       5/50 (10%)      2/50 (4%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |     10.8%           14.1%            8.5%          |      4.2%            2.9%            0.0%          |
|TERMINAL (d)           |     4/37 (11%)      4/34 (12%)      1/22 (5%)      |     1/24 (4%)       1/35 (3%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         694             723           |      729 (T)         729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.486N        P=0.446         P=0.585N       |     P=0.436N        P=0.676N        P=0.547N       |
|INCIDENTAL TUMOR       |     P=0.351N        P=0.462         P=0.479N       |     P=0.436N        P=0.676N        P=0.547N       |
|LOGISTIC REGRESSION    |     P=0.383N        P=0.442         P=0.547N       |     P=0.436N        P=0.676N        P=0.547N       |
|COCHRAN-ARMITAGE       |     P=0.240N                                       |     P=0.364N                                       |
|FISHER EXACT           |                     P=0.500         P=0.339N       |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  12
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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)            |     5/50 (10%)      3/50 (6%)       3/50 (6%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     12.2%            8.6%           11.1%          |      4.2%            0.0%            0.0%          |
|TERMINAL (d)           |     3/37 (8%)       2/34 (6%)       1/22 (5%)      |     1/24 (4%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      610             723             670           |      729 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.599N        P=0.404N        P=0.576N       |     P=0.520N        P=0.425N        P=0.547N       |
|INCIDENTAL TUMOR       |     P=0.303N        P=0.388N        P=0.302N       |     P=0.520N        P=0.425N        P=0.547N       |
|LOGISTIC REGRESSION    |     P=0.425N        P=0.371N        P=0.394N       |     P=0.520N        P=0.425N        P=0.547N       |
|COCHRAN-ARMITAGE       |     P=0.368N                                       |     P=0.461N                                       |
|FISHER EXACT           |                     P=0.357N        P=0.357N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.1%            2.9%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       1/34 (3%)       0/22 (0%)      |     0/24 (0%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      447             730 (T)         ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.234N        P=0.517N        P=0.252N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.128N        P=0.399N        P=0.065N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.149N        P=0.456N        P=0.154N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.195N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  13
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)      5/50 (10%)      5/50 (10%)     |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     15.8%           13.6%           16.7%          |      4.2%            0.0%            0.0%          |
|TERMINAL (d)           |     3/37 (8%)       3/34 (9%)       1/22 (5%)      |     1/24 (4%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      447             664             670           |      729 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.550         P=0.433N        P=0.598N       |     P=0.520N        P=0.425N        P=0.547N       |
|INCIDENTAL TUMOR       |     P=0.198N        P=0.348N        P=0.162N       |     P=0.520N        P=0.425N        P=0.547N       |
|LOGISTIC REGRESSION    |     P=0.379N        P=0.353N        P=0.333N       |     P=0.520N        P=0.425N        P=0.547N       |
|COCHRAN-ARMITAGE       |     P=0.391N                                       |     P=0.461N                                       |
|FISHER EXACT           |                     P=0.380N        P=0.380N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.1%            5.4%            6.3%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       1/34 (3%)       0/22 (0%)      |     0/24 (0%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      447             664             700           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.562         P=0.674         P=0.634        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.381N        P=0.607N        P=0.357N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.583N        P=0.661N        P=0.615N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.643                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.691N        P=0.691N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  14
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                        |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            2.5%            6.3%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       0/34 (0%)       0/22 (0%)      |     0/24 (0%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             664             700           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.154         P=0.490         P=0.184        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.429         P=0.527         P=0.432        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.189         P=0.509         P=0.216        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.195                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    45/49 (92%)     39/44 (89%)     44/50 (88%)     |                                                    |
|ADJUSTED (b)           |    100.0%          100.0%           97.8%          |                                                    |
|TERMINAL (d)           |    36/36 (100%)    29/29 (100%)    21/22 (95%)     |                                                    |
|FIRST INCIDENCE (DAYS) |      551             503             499           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.433         P=0.003 **     |                                                    |
|INCIDENTAL TUMOR       |     P=0.391         P=0.475         P=0.459        |                                                    |
|LOGISTIC REGRESSION    |     P=0.354         P=0.551         P=0.466        |                                                    |
|COCHRAN-ARMITAGE       |     P=0.382N                                       |                                                    |
|FISHER EXACT           |                     P=0.431N        P=0.383N       |                                                    |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  15
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     9/49 (18%)      3/12 (25%)     10/49 (20%)     |     9/49 (18%)      3/50 (6%)       1/47 (2%)      |
|ADJUSTED (b)           |     24.3%          100.0%           35.7%          |     28.3%            8.2%            5.3%          |
|TERMINAL (d)           |     9/37 (24%)      3/3 (100%)      6/22 (27%)     |     3/23 (13%)      2/35 (6%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         574           |      635             721             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.115         P=0.019 *       P=0.130        |     P=0.032N*       P=0.021N*       P=0.031N*      |
|INCIDENTAL TUMOR       |     P=0.241         P=0.019 *       P=0.246        |     P=0.023N*       P=0.120N        P=0.022N*      |
|LOGISTIC REGRESSION    |     P=0.365         P=0.019 *       P=0.355        |     P=0.023N*       P=0.040N*       P=0.021N*      |
|COCHRAN-ARMITAGE       |     P=0.505                                        |     P=0.014N*                                      |
|FISHER EXACT           |                     P=0.435         P=0.500        |                     P=0.056N        P=0.009N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/49 (2%)       0/12 (0%)       0/49 (0%)      |     3/49 (6%)       1/50 (2%)       2/47 (4%)      |
|ADJUSTED (b)           |      2.7%            0.0%            0.0%          |     11.2%            2.9%            9.1%          |
|TERMINAL (d)           |     1/37 (3%)       0/3 (0%)        0/22 (0%)      |     2/23 (9%)       1/35 (3%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         ---             ---           |      651             729 (T)         698           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.507N        P=0.947N        P=0.604N       |     P=0.615         P=0.195N        P=0.606N       |
|INCIDENTAL TUMOR       |     P=0.507N        P=0.947N        P=0.604N       |     P=0.641         P=0.260N        P=0.626N       |
|LOGISTIC REGRESSION    |     P=0.507N        P=0.947N        P=0.604N       |     P=0.645         P=0.261N        P=0.595N       |
|COCHRAN-ARMITAGE       |     P=0.419N                                       |     P=0.571N                                       |
|FISHER EXACT           |                     P=0.803N        P=0.500N       |                     P=0.301N        P=0.520N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  16
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     9/49 (18%)      3/12 (25%)     10/49 (20%)     |    12/49 (24%)      4/50 (8%)       3/47 (6%)      |
|ADJUSTED (b)           |     24.3%          100.0%           35.7%          |     37.2%           11.0%           13.9%          |
|TERMINAL (d)           |     9/37 (24%)      3/3 (100%)      6/22 (27%)     |     5/23 (22%)      3/35 (9%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      730 (T)         730 (T)         574           |      635             721             698           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.115         P=0.019 *       P=0.130        |     P=0.069N        P=0.006N**      P=0.049N*      |
|INCIDENTAL TUMOR       |     P=0.241         P=0.019 *       P=0.246        |     P=0.043N*       P=0.046N*       P=0.034N*      |
|LOGISTIC REGRESSION    |     P=0.365         P=0.019 *       P=0.355        |     P=0.046N*       P=0.015N*       P=0.031N*      |
|COCHRAN-ARMITAGE       |     P=0.505                                        |     P=0.025N*                                      |
|FISHER EXACT           |                     P=0.435         P=0.500        |                     P=0.024N*       P=0.014N*      |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/49 (0%)       0/12 (0%)       2/49 (4%)      |     1/49 (2%)       1/50 (2%)       1/47 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%            6.9%          |      4.3%            2.9%            5.3%          |
|TERMINAL (d)           |     0/37 (0%)       0/3 (0%)        1/22 (5%)      |     1/23 (4%)       1/35 (3%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             588           |      729 (T)         729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.086           (e)           P=0.171        |     P=0.624         P=0.665N        P=0.720        |
|INCIDENTAL TUMOR       |     P=0.130           (e)           P=0.222        |     P=0.624         P=0.665N        P=0.720        |
|LOGISTIC REGRESSION    |     P=0.157           (e)           P=0.253        |     P=0.624         P=0.665N        P=0.720        |
|COCHRAN-ARMITAGE       |     P=0.155                                        |     P=0.685                                        |
|FISHER EXACT           |                       (e)           P=0.247        |                     P=0.747N        P=0.742        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  17
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     7/50 (14%)     10/50 (20%)      9/50 (18%)     |
|ADJUSTED (b)           |                                                    |     20.4%           23.9%           34.8%          |
|TERMINAL (d)           |                                                    |     2/24 (8%)       5/35 (14%)      5/19 (26%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      510             551             495           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.194         P=0.497         P=0.232        |
|INCIDENTAL TUMOR       |                                                    |     P=0.351         P=0.159         P=0.271        |
|LOGISTIC REGRESSION    |                                                    |     P=0.360         P=0.297         P=0.304        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.441                                        |
|FISHER EXACT           |                                                    |                     P=0.298         P=0.393        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     1/50 (2%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |                                                    |      2.2%            0.0%            6.5%          |
|TERMINAL (d)           |                                                    |     0/24 (0%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      544             ---             605           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.235         P=0.496N        P=0.422        |
|INCIDENTAL TUMOR       |                                                    |     P=0.335         P=0.773N        P=0.469        |
|LOGISTIC REGRESSION    |                                                    |     P=0.356         P=0.448N        P=0.553        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.303                                        |
|FISHER EXACT           |                                                    |                     P=0.500N        P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  18
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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            |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     8/50 (16%)     10/50 (20%)     11/50 (22%)     |
|ADJUSTED (b)           |                                                    |     22.2%           23.9%           39.0%          |
|TERMINAL (d)           |                                                    |     2/24 (8%)       5/35 (14%)      5/19 (26%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      510             551             495           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.107         P=0.595         P=0.162        |
|INCIDENTAL TUMOR       |                                                    |     P=0.236         P=0.190         P=0.192        |
|LOGISTIC REGRESSION    |                                                    |     P=0.254         P=0.397         P=0.244        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.306                                        |
|FISHER EXACT           |                                                    |                     P=0.398         P=0.306        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)     10/50 (20%)      7/50 (14%)     |    15/50 (30%)     17/50 (34%)     17/50 (34%)     |
|ADJUSTED (b)           |     16.2%           22.9%           20.3%          |     40.1%           41.6%           58.4%          |
|TERMINAL (d)           |     6/37 (16%)      3/34 (9%)       2/22 (9%)      |     5/24 (21%)     12/35 (34%)      8/19 (42%)     |
|FIRST INCIDENCE (DAYS) |      730 (T)         462             491           |      510              97             495           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.338         P=0.180         P=0.242        |     P=0.106         P=0.418N        P=0.187        |
|INCIDENTAL TUMOR       |     P=0.352N        P=0.333         P=0.535        |     P=0.263         P=0.341         P=0.197        |
|LOGISTIC REGRESSION    |     P=0.482N        P=0.229         P=0.516        |     P=0.298         P=0.413         P=0.252        |
|COCHRAN-ARMITAGE       |     P=0.562N                                       |     P=0.426                                        |
|FISHER EXACT           |                     P=0.207         P=0.500        |                     P=0.415         P=0.415        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  19
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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 And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       1/50 (2%)       3/50 (6%)      |
|ADJUSTED (b)           |      0.0%            0.0%            2.2%          |      0.0%            2.9%           12.7%          |
|TERMINAL (d)           |     0/37 (0%)       0/34 (0%)       0/22 (0%)      |     0/24 (0%)       1/35 (3%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             499           |      ---             729 (T)         670           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.304           (e)           P=0.492        |     P=0.031 *       P=0.575         P=0.090        |
|INCIDENTAL TUMOR       |     P=0.475           (e)           P=0.814        |     P=0.044 *       P=0.575         P=0.073        |
|LOGISTIC REGRESSION    |     P=0.352           (e)           P=0.560        |     P=0.041 *       P=0.575         P=0.086        |
|COCHRAN-ARMITAGE       |     P=0.311                                        |     P=0.075                                        |
|FISHER EXACT           |                       (e)           P=0.500        |                     P=0.500         P=0.121        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            0.0%            2.2%          |      0.0%            0.0%            9.2%          |
|TERMINAL (d)           |     0/37 (0%)       0/34 (0%)       0/22 (0%)      |     0/24 (0%)       0/35 (0%)       1/19 (5%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             499           |      ---             ---             695           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.304           (e)           P=0.492        |     P=0.048 *         (e)           P=0.195        |
|INCIDENTAL TUMOR       |     P=0.475           (e)           P=0.814        |     P=0.065           (e)           P=0.180        |
|LOGISTIC REGRESSION    |     P=0.352           (e)           P=0.560        |     P=0.056           (e)           P=0.187        |
|COCHRAN-ARMITAGE       |     P=0.311                                        |     P=0.092                                        |
|FISHER EXACT           |                       (e)           P=0.500        |                       (e)           P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  20
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      2/50 (4%)       5/50 (10%)     |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     12.2%            5.1%           15.8%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/37 (5%)       1/34 (3%)       1/22 (5%)      |     0/24 (0%)       0/35 (0%)       0/19 (0%)      |
|FIRST INCIDENCE (DAYS) |      653             616             600           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.267         P=0.261N        P=0.396        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.512N        P=0.224N        P=0.388N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.450         P=0.220N        P=0.604        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.465                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.218N        P=0.630N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    47/50 (94%)     46/50 (92%)     47/50 (94%)     |    41/50 (82%)     39/50 (78%)     29/50 (58%)     |
|ADJUSTED (b)           |    100.0%           97.9%          100.0%          |     93.0%           81.3%           84.6%          |
|TERMINAL (d)           |    37/37 (100%)    33/34 (97%)     22/22 (100%)    |    21/24 (88%)     26/35 (74%)     14/19 (74%)     |
|FIRST INCIDENCE (DAYS) |      551             462             491           |      510             537             495           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.356         P<0.001 **     |     P=0.481N        P=0.030N*       P=0.332N       |
|INCIDENTAL TUMOR       |     P=0.191         P=0.541         P=0.153        |     P=0.057N        P=0.518N        P=0.093N       |
|LOGISTIC REGRESSION    |     P=0.156         P=0.696         P=0.214        |     P=0.071N        P=0.394N        P=0.099N       |
|COCHRAN-ARMITAGE       |     P=0.564                                        |     P=0.003N**                                     |
|FISHER EXACT           |                     P=0.500N        P=0.661N       |                     P=0.402N        P=0.008N**     |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  21
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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%)     23/50 (46%)     21/50 (42%)     |    27/50 (54%)     21/50 (42%)     24/50 (48%)     |
|ADJUSTED (b)           |     35.0%           50.4%           49.7%          |     63.3%           51.7%           72.2%          |
|TERMINAL (d)           |    10/37 (27%)     12/34 (35%)      4/22 (18%)     |    10/24 (42%)     16/35 (46%)     10/19 (53%)     |
|FIRST INCIDENCE (DAYS) |      447             462             372           |      495              97             495           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.041 *       P=0.066         P=0.029 *      |     P=0.167         P=0.033N*       P=0.383        |
|INCIDENTAL TUMOR       |     P=0.447N        P=0.148         P=0.544        |     P=0.385         P=0.274N        P=0.415        |
|LOGISTIC REGRESSION    |     P=0.537         P=0.114         P=0.380        |     P=0.471         P=0.161N        P=0.567        |
|COCHRAN-ARMITAGE       |     P=0.240                                        |     P=0.443N                                       |
|FISHER EXACT           |                     P=0.074         P=0.149        |                     P=0.158N        P=0.345N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    48/50 (96%)     48/50 (96%)     48/50 (96%)     |    49/50 (98%)     46/50 (92%)     37/50 (74%)     |
|ADJUSTED (b)           |    100.0%           98.0%          100.0%          |     98.0%           93.9%           94.8%          |
|TERMINAL (d)           |    37/37 (100%)    33/34 (97%)     22/22 (100%)    |    23/24 (96%)     32/35 (91%)     17/19 (89%)     |
|FIRST INCIDENCE (DAYS) |      447             462             372           |      354              97             495           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.293         P=0.001 **     |     P=0.446         P=0.012N*       P=0.444N       |
|INCIDENTAL TUMOR       |     P=0.565         P=0.755         P=0.480        |     P=0.008N**      P=0.333N        P=0.022N*      |
|LOGISTIC REGRESSION    |     P=0.446         P=0.652         P=0.505        |     P=0.010N*       P=0.201N        P=0.028N*      |
|COCHRAN-ARMITAGE       |     P=0.643                                        |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.691N        P=0.691N       |                     P=0.181N        P<0.001N**     |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05030 TEST: 01                                                 PAGE  22
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 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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