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TDMS Study 05058-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                    ROXARSONE                                       DATE: 09/08/94       
EXPERIMENT: 05058 TEST: 01                                                                                     TIME: 07:46:37       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NOI-ES-28024          ROUTE: DOSED FEED                                                                  NTP C#: C56508       
PATHOLOGIST: H. GILES                                                                                          CAS: 121-19-7        
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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: Southern Research Inst                                    ROXARSONE                                       DATE: 09/08/94      
EXPERIMENT: 05058 TEST: 01                                                                                     TIME: 07:46:37      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NOI-ES-28024          ROUTE: DOSED FEED                                                                  NTP C#: C56508      
PATHOLOGIST: H. GILES                                                                                          CAS: 121-19-7       
 
 
 
 
 
                                                    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: Southern Research Inst                                    ROXARSONE                                       DATE: 09/08/94       
EXPERIMENT: 05058 TEST: 01                                                                                     TIME: 07:46:37       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NOI-ES-28024          ROUTE: DOSED FEED                                                                  NTP C#: C56508       
PATHOLOGIST: H. GILES                                                                                          CAS: 121-19-7        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                           IN THE ANALYSIS OF THE STUDY OF ROXARSONE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Bone                          Osteosarcoma
                             Islets, Pancreatic            Adenoma
                             Pancreas                      Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Osteosarcoma
                                                           Osteosarcoma or Osteoma
                                                           Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                             Mammary Gland                 Carcinoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
 
              ====================================================================================================
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   1
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/50 (30%)     14/49 (29%)     16/50 (32%)     |     0/49 (0%)       1/48 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |     43.5%           47.6%           61.1%          |      0.0%            2.9%            4.7%          |
|TERMINAL (d)           |     7/24 (29%)      5/18 (28%)      9/18 (50%)     |     0/26 (0%)       1/34 (3%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      616             629             637           |      ---             729 (T)         677           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.274         P=0.449         P=0.295        |     P=0.173         P=0.554         P=0.280        |
|INCIDENTAL TUMOR       |     P=0.469         P=0.550N        P=0.488        |     P=0.183         P=0.554         P=0.253        |
|LOGISTIC REGRESSION    |     P=0.449         P=0.546N        P=0.491        |     P=0.151         P=0.554         P=0.239        |
|COCHRAN-ARMITAGE       |     P=0.457                                        |     P=0.146                                        |
|FISHER EXACT           |                     P=0.526N        P=0.500        |                     P=0.495         P=0.253        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      4/49 (8%)       4/50 (8%)      |     0/49 (0%)       0/48 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     17.1%           18.9%           14.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       3/18 (17%)      0/18 (0%)      |     0/26 (0%)       0/34 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      675             637             671           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.530N        P=0.628N        P=0.586N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.379N        P=0.565N        P=0.363N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.441N        P=0.545N        P=0.508N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.430N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.513N        P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   2
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    19/50 (38%)     16/49 (33%)     17/50 (34%)     |     0/49 (0%)       1/48 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |     51.9%           55.7%           62.7%          |      0.0%            2.9%            4.7%          |
|TERMINAL (d)           |     8/24 (33%)      7/18 (39%)      9/18 (50%)     |     0/26 (0%)       1/34 (3%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      616             629             637           |      ---             729 (T)         677           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.461         P=0.553         P=0.494        |     P=0.173         P=0.554         P=0.280        |
|INCIDENTAL TUMOR       |     P=0.347N        P=0.407N        P=0.379N       |     P=0.183         P=0.554         P=0.253        |
|LOGISTIC REGRESSION    |     P=0.385N        P=0.393N        P=0.426N       |     P=0.151         P=0.554         P=0.239        |
|COCHRAN-ARMITAGE       |     P=0.376N                                       |     P=0.146                                        |
|FISHER EXACT           |                     P=0.365N        P=0.418N       |                     P=0.495         P=0.253        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      7.5%            0.0%            0.0%          |      0.0%            0.0%            5.8%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      283             ---             ---           |      ---             ---             724           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.041N*       P=0.133N        P=0.130N       |     P=0.112           (e)           P=0.287        |
|INCIDENTAL TUMOR       |     P=0.065N        P=0.223N        P=0.161N       |     P=0.121           (e)           P=0.268        |
|LOGISTIC REGRESSION    |     P=0.061N        P=0.146N        P=0.196N       |     P=0.112           (e)           P=0.280        |
|COCHRAN-ARMITAGE       |     P=0.037N*                                      |     P=0.095                                        |
|FISHER EXACT           |                     P=0.121N        P=0.121N       |                       (e)           P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   3
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/49 (14%)      3/48 (6%)       2/48 (4%)      |     1/44 (2%)       3/47 (6%)       6/48 (13%)     |
|ADJUSTED (b)           |     23.0%           11.1%            8.0%          |      4.2%            8.9%           16.8%          |
|TERMINAL (d)           |     4/24 (17%)      1/17 (6%)       1/17 (6%)      |     1/24 (4%)       2/32 (6%)       3/30 (10%)     |
|FIRST INCIDENCE (DAYS) |      581             637             630           |      729 (T)         728             530           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.089N        P=0.261N        P=0.141N       |     P=0.057         P=0.410         P=0.100        |
|INCIDENTAL TUMOR       |     P=0.068N        P=0.178N        P=0.121N       |     P=0.070         P=0.311         P=0.116        |
|LOGISTIC REGRESSION    |     P=0.051N        P=0.166N        P=0.085N       |     P=0.049 *       P=0.393         P=0.074        |
|COCHRAN-ARMITAGE       |     P=0.052N                                       |     P=0.045 *                                      |
|FISHER EXACT           |                     P=0.167N        P=0.084N       |                     P=0.334         P=0.070        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/49 (0%)       4/48 (8%)       0/48 (0%)      |     1/44 (2%)       1/47 (2%)       1/48 (2%)      |
|ADJUSTED (b)           |      0.0%           13.7%            0.0%          |      3.0%            2.0%            3.3%          |
|TERMINAL (d)           |     0/24 (0%)       1/17 (6%)       0/17 (0%)      |     0/24 (0%)       0/32 (0%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             581             ---           |      701             486             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.580         P=0.052           (e)          |     P=0.606N        P=0.745N        P=0.716N       |
|INCIDENTAL TUMOR       |     P=0.597N        P=0.065           (e)          |     P=0.556N        P=0.755N        P=0.716N       |
|LOGISTIC REGRESSION    |     P=0.623N        P=0.067           (e)          |     P=0.605N        P=0.687N        P=0.730N       |
|COCHRAN-ARMITAGE       |     P=0.615                                        |     P=0.617N                                       |
|FISHER EXACT           |                     P=0.056           (e)          |                     P=0.736N        P=0.731N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   4
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/49 (14%)      7/48 (15%)      2/48 (4%)      |     2/44 (5%)       4/47 (9%)       7/48 (15%)     |
|ADJUSTED (b)           |     23.0%           23.6%            8.0%          |      7.1%           10.7%           19.9%          |
|TERMINAL (d)           |     4/24 (17%)      2/17 (12%)      1/17 (6%)      |     1/24 (4%)       2/32 (6%)       4/30 (13%)     |
|FIRST INCIDENCE (DAYS) |      581             581             630           |      701             486             530           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.132N        P=0.469         P=0.141N       |     P=0.091         P=0.438         P=0.142        |
|INCIDENTAL TUMOR       |     P=0.090N        P=0.589         P=0.121N       |     P=0.112         P=0.359         P=0.158        |
|LOGISTIC REGRESSION    |     P=0.075N        P=0.613         P=0.085N       |     P=0.070         P=0.370         P=0.106        |
|COCHRAN-ARMITAGE       |     P=0.077N                                       |     P=0.070                                        |
|FISHER EXACT           |                     P=0.597         P=0.084N       |                     P=0.371         P=0.101        |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Jejunum                                                                                                         |
|     Leiomyosarcoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            8.6%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       1/18 (6%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             681             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.631         P=0.205           (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.658N        P=0.214           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.663         P=0.224           (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.669                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.247           (e)          |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   5
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       4/50 (8%)      |     1/50 (2%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%           11.6%           12.0%          |      2.9%            5.7%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       1/18 (6%)       0/18 (0%)      |     0/27 (0%)       2/35 (6%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             681             638           |      687             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.046 *       P=0.102         P=0.063        |     P=0.318N        P=0.569         P=0.473N       |
|INCIDENTAL TUMOR       |     P=0.078         P=0.111         P=0.102        |     P=0.328N        P=0.463         P=0.484N       |
|LOGISTIC REGRESSION    |     P=0.049 *       P=0.114         P=0.060        |     P=0.335N        P=0.518         P=0.502N       |
|COCHRAN-ARMITAGE       |     P=0.049 *                                      |     P=0.360N                                       |
|FISHER EXACT           |                     P=0.121         P=0.059        |                     P=0.500         P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      7.3%            5.0%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      695             723             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.184N        P=0.579N        P=0.292N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.123N        P=0.519N        P=0.229N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.154N        P=0.535N        P=0.246N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.142N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   6
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       4/50 (8%)       4/50 (8%)      |     1/50 (2%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |      7.3%           16.1%           12.0%          |      2.9%            5.7%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       1/18 (6%)       0/18 (0%)      |     0/27 (0%)       2/35 (6%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      695             681             638           |      687             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.233         P=0.264         P=0.299        |     P=0.318N        P=0.569         P=0.473N       |
|INCIDENTAL TUMOR       |     P=0.370         P=0.310         P=0.428        |     P=0.328N        P=0.463         P=0.484N       |
|LOGISTIC REGRESSION    |     P=0.274         P=0.307         P=0.337        |     P=0.335N        P=0.518         P=0.502N       |
|COCHRAN-ARMITAGE       |     P=0.274                                        |     P=0.360N                                       |
|FISHER EXACT           |                     P=0.339         P=0.339        |                     P=0.500         P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      3.1%           11.1%            5.6%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       2/18 (11%)      1/18 (6%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      693             729 (T)         729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.532         P=0.414         P=0.704        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.579         P=0.440         P=0.755N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.592         P=0.463         P=0.755        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.622N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.753N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   7
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      7.2%           11.1%            5.6%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       2/18 (11%)      1/18 (6%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      693             729 (T)         729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.494N        P=0.599         P=0.590N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.451N        P=0.621         P=0.525N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.429N        P=0.654         P=0.525N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.390N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.691N        P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            4.6%            0.0%          |      0.0%            2.9%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       1/35 (3%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             580             ---           |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.657N        P=0.234           (e)          |     P=0.714N        P=0.552           (e)          |
|INCIDENTAL TUMOR       |     P=0.683         P=0.328           (e)          |     P=0.714N        P=0.552           (e)          |
|LOGISTIC REGRESSION    |     P=0.604         P=0.204           (e)          |     P=0.714N        P=0.552           (e)          |
|COCHRAN-ARMITAGE       |     P=0.669                                        |     P=0.731                                        |
|FISHER EXACT           |                     P=0.247           (e)          |                     P=0.500           (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   8
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      6.1%            0.0%            4.5%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      671             ---             723           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.393N        P=0.266N        P=0.536N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.266N        P=0.223N        P=0.373N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.363N        P=0.239N        P=0.502N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.360N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular 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)           |      6.1%            4.6%            4.5%          |      0.0%            2.9%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       1/35 (3%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      671             580             723           |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.410N        P=0.666         P=0.536N       |     P=0.714N        P=0.552           (e)          |
|INCIDENTAL TUMOR       |     P=0.309N        P=0.610N        P=0.373N       |     P=0.714N        P=0.552           (e)          |
|LOGISTIC REGRESSION    |     P=0.406N        P=0.691         P=0.502N       |     P=0.714N        P=0.552           (e)          |
|COCHRAN-ARMITAGE       |     P=0.390N                                       |     P=0.731                                        |
|FISHER EXACT           |                     P=0.691N        P=0.500N       |                     P=0.500           (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE   9
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      6.1%            4.6%            4.5%          |      0.0%            2.9%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       1/35 (3%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      671             580             723           |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.410N        P=0.666         P=0.536N       |     P=0.714N        P=0.552           (e)          |
|INCIDENTAL TUMOR       |     P=0.309N        P=0.610N        P=0.373N       |     P=0.714N        P=0.552           (e)          |
|LOGISTIC REGRESSION    |     P=0.406N        P=0.691         P=0.502N       |     P=0.714N        P=0.552           (e)          |
|COCHRAN-ARMITAGE       |     P=0.390N                                       |     P=0.731                                        |
|FISHER EXACT           |                     P=0.691N        P=0.500N       |                     P=0.500           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/50 (4%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      8.3%            8.0%            0.0%          |      0.0%            0.0%            3.1%          |
|TERMINAL (d)           |     2/24 (8%)       1/18 (6%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         633             ---           |      ---             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.229N        P=0.608         P=0.303N       |     P=0.286           (e)           P=0.534        |
|INCIDENTAL TUMOR       |     P=0.227N        P=0.655         P=0.303N       |     P=0.286           (e)           P=0.534        |
|LOGISTIC REGRESSION    |     P=0.182N        P=0.675         P=0.303N       |     P=0.286           (e)           P=0.534        |
|COCHRAN-ARMITAGE       |     P=0.176N                                       |     P=0.269                                        |
|FISHER EXACT           |                     P=0.691N        P=0.247N       |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  10
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     4/50 (8%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      9.9%            0.0%            2.3%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     1/27 (4%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      404             ---             678           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.072N        P=0.058N        P=0.159N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.074N        P=0.048N*       P=0.157N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.078N        P=0.054N        P=0.183N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.082N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.059N        P=0.181N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       3/50 (6%)      |    21/50 (42%)     17/50 (34%)     21/50 (42%)     |
|ADJUSTED (b)           |      6.1%            0.0%           13.1%          |     58.5%           42.5%           56.2%          |
|TERMINAL (d)           |     1/24 (4%)       0/18 (0%)       1/18 (6%)      |    13/27 (48%)     12/35 (34%)     16/32 (50%)     |
|FIRST INCIDENCE (DAYS) |      538             ---             695           |      526             685             685           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.332         P=0.276N        P=0.422        |     P=0.311N        P=0.097N        P=0.326N       |
|INCIDENTAL TUMOR       |     P=0.399         P=0.151N        P=0.513        |     P=0.362N        P=0.314N        P=0.409N       |
|LOGISTIC REGRESSION    |     P=0.390         P=0.244N        P=0.498        |     P=0.406N        P=0.230N        P=0.463N       |
|COCHRAN-ARMITAGE       |     P=0.390                                        |     P=0.541                                        |
|FISHER EXACT           |                     P=0.247N        P=0.500        |                     P=0.268N        P=0.580N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  11
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       3/50 (6%)      |    24/50 (48%)     17/50 (34%)     22/50 (44%)     |
|ADJUSTED (b)           |      6.1%            0.0%           13.1%          |     61.2%           42.5%           57.2%          |
|TERMINAL (d)           |     1/24 (4%)       0/18 (0%)       1/18 (6%)      |    13/27 (48%)     12/35 (34%)     16/32 (50%)     |
|FIRST INCIDENCE (DAYS) |      538             ---             695           |      404             685             678           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.332         P=0.276N        P=0.422        |     P=0.195N        P=0.038N*       P=0.212N       |
|INCIDENTAL TUMOR       |     P=0.399         P=0.151N        P=0.513        |     P=0.218N        P=0.132N        P=0.258N       |
|LOGISTIC REGRESSION    |     P=0.390         P=0.244N        P=0.498        |     P=0.320N        P=0.105N        P=0.392N       |
|COCHRAN-ARMITAGE       |     P=0.390                                        |     P=0.381N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.500        |                     P=0.111N        P=0.421N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      7.2%            0.0%            2.8%          |      2.9%            0.0%            2.7%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      703             ---             671           |      700             ---             723           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.395N        P=0.270N        P=0.541N       |     P=0.626N        P=0.478N        P=0.714N       |
|INCIDENTAL TUMOR       |     P=0.266N        P=0.223N        P=0.373N       |     P=0.634N        P=0.674N        P=0.747N       |
|LOGISTIC REGRESSION    |     P=0.362N        P=0.253N        P=0.501N       |     P=0.653N        P=0.497N        P=0.747N       |
|COCHRAN-ARMITAGE       |     P=0.360N                                       |     P=0.669N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                     P=0.500N        P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  12
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      7.2%            0.0%            2.8%          |      2.9%            0.0%            2.7%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      703             ---             671           |      700             ---             723           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.395N        P=0.270N        P=0.541N       |     P=0.626N        P=0.478N        P=0.714N       |
|INCIDENTAL TUMOR       |     P=0.266N        P=0.223N        P=0.373N       |     P=0.634N        P=0.674N        P=0.747N       |
|LOGISTIC REGRESSION    |     P=0.362N        P=0.253N        P=0.501N       |     P=0.653N        P=0.497N        P=0.747N       |
|COCHRAN-ARMITAGE       |     P=0.360N                                       |     P=0.669N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                     P=0.500N        P=0.753N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/50 (2%)       5/50 (10%)     |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%            5.6%           18.8%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       1/18 (6%)       1/18 (6%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         664           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.035 *       P=0.697         P=0.075        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.061         P=0.697         P=0.136        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.046 *       P=0.697         P=0.099        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.049 *                                      |       (e)                                          |
|FISHER EXACT           |                     P=0.753N        P=0.102        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  13
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pharynx                                                                                                                          |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      7.2%            0.0%            2.8%          |      2.9%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      703             ---             671           |      700             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.395N        P=0.270N        P=0.541N       |     P=0.250N        P=0.478N        P=0.473N       |
|INCIDENTAL TUMOR       |     P=0.266N        P=0.223N        P=0.373N       |     P=0.279N        P=0.674N        P=0.484N       |
|LOGISTIC REGRESSION    |     P=0.362N        P=0.253N        P=0.501N       |     P=0.265N        P=0.497N        P=0.495N       |
|COCHRAN-ARMITAGE       |     P=0.360N                                       |     P=0.269N                                       |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)     13/48 (27%)      8/48 (17%)     |    27/50 (54%)     28/49 (57%)     18/48 (38%)     |
|ADJUSTED (b)           |     21.4%           49.3%           34.4%          |     69.5%           67.7%           46.5%          |
|TERMINAL (d)           |     4/24 (17%)      7/18 (39%)      4/17 (24%)     |    16/27 (59%)     21/34 (62%)     11/31 (35%)     |
|FIRST INCIDENCE (DAYS) |      616             495             671           |      485             486             678           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.188         P=0.026 *       P=0.224        |     P=0.019N*       P=0.320N        P=0.025N*      |
|INCIDENTAL TUMOR       |     P=0.266         P=0.044 *       P=0.323        |     P=0.031N*       P=0.576         P=0.043N*      |
|LOGISTIC REGRESSION    |     P=0.307         P=0.049 *       P=0.325        |     P=0.049N*       P=0.463         P=0.060N       |
|COCHRAN-ARMITAGE       |     P=0.313                                        |     P=0.065N                                       |
|FISHER EXACT           |                     P=0.051         P=0.355        |                     P=0.455         P=0.075N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  14
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)     13/48 (27%)      8/48 (17%)     |    28/50 (56%)     28/49 (57%)     18/48 (38%)     |
|ADJUSTED (b)           |     21.4%           49.3%           34.4%          |     70.4%           67.7%           46.5%          |
|TERMINAL (d)           |     4/24 (17%)      7/18 (39%)      4/17 (24%)     |    16/27 (59%)     21/34 (62%)     11/31 (35%)     |
|FIRST INCIDENCE (DAYS) |      616             495             671           |      485             486             678           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.188         P=0.026 *       P=0.224        |     P=0.013N*       P=0.260N        P=0.017N*      |
|INCIDENTAL TUMOR       |     P=0.266         P=0.044 *       P=0.323        |     P=0.019N*       P=0.541N        P=0.027N*      |
|LOGISTIC REGRESSION    |     P=0.307         P=0.049 *       P=0.325        |     P=0.032N*       P=0.544         P=0.039N*      |
|COCHRAN-ARMITAGE       |     P=0.313                                        |     P=0.043N*                                      |
|FISHER EXACT           |                     P=0.051         P=0.355        |                     P=0.535         P=0.051N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       4/50 (8%)       4/50 (8%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     13.3%           13.7%           13.7%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       1/18 (6%)       1/18 (6%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      651             633             651           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.504         P=0.558         P=0.572        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.504N        P=0.629         P=0.579N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.571N        P=0.637         P=0.642N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.573                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.643N        P=0.643N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  15
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.1%            0.0%           11.1%          |      0.0%            0.0%            3.1%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       2/18 (11%)     |     0/27 (0%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      564             ---             729 (T)       |      ---             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.312         P=0.504N        P=0.434        |     P=0.286           (e)           P=0.534        |
|INCIDENTAL TUMOR       |     P=0.307         P=0.419N        P=0.434        |     P=0.286           (e)           P=0.534        |
|LOGISTIC REGRESSION    |     P=0.357         P=0.559N        P=0.494        |     P=0.286           (e)           P=0.534        |
|COCHRAN-ARMITAGE       |     P=0.360                                        |     P=0.269                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500        |                       (e)           P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%           11.1%          |      0.0%            0.0%            3.1%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       2/18 (11%)     |     0/27 (0%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             729 (T)       |      ---             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.072           (e)           P=0.176        |     P=0.286           (e)           P=0.534        |
|INCIDENTAL TUMOR       |     P=0.072           (e)           P=0.176        |     P=0.286           (e)           P=0.534        |
|LOGISTIC REGRESSION    |     P=0.072           (e)           P=0.176        |     P=0.286           (e)           P=0.534        |
|COCHRAN-ARMITAGE       |     P=0.095                                        |     P=0.269                                        |
|FISHER EXACT           |                       (e)           P=0.247        |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  16
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      5/50 (10%)      6/50 (12%)     |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |     15.1%           18.8%           23.8%          |      0.0%            2.9%            6.3%          |
|TERMINAL (d)           |     2/24 (8%)       2/18 (11%)      3/18 (17%)     |     0/27 (0%)       1/35 (3%)       2/32 (6%)      |
|FIRST INCIDENCE (DAYS) |      564             633             651           |      ---             729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.347         P=0.532         P=0.404        |     P=0.161         P=0.552         P=0.276        |
|INCIDENTAL TUMOR       |     P=0.458         P=0.624         P=0.523        |     P=0.161         P=0.552         P=0.276        |
|LOGISTIC REGRESSION    |     P=0.438         P=0.631         P=0.501        |     P=0.161         P=0.552         P=0.276        |
|COCHRAN-ARMITAGE       |     P=0.436                                        |     P=0.142                                        |
|FISHER EXACT           |                     P=0.630N        P=0.500        |                     P=0.500         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/50 (2%)       3/50 (6%)      |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      3.1%            5.6%           12.1%          |      3.7%            0.0%            3.1%          |
|TERMINAL (d)           |     0/24 (0%)       1/18 (6%)       1/18 (6%)      |     1/27 (4%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      693             729 (T)         581           |      729 (T)         ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.159         P=0.709         P=0.249        |     P=0.638N        P=0.448N        P=0.724N       |
|INCIDENTAL TUMOR       |     P=0.211         P=0.736         P=0.345        |     P=0.638N        P=0.448N        P=0.724N       |
|LOGISTIC REGRESSION    |     P=0.203         P=0.746         P=0.304        |     P=0.638N        P=0.448N        P=0.724N       |
|COCHRAN-ARMITAGE       |     P=0.202                                        |     P=0.669N                                       |
|FISHER EXACT           |                     P=0.753N        P=0.309        |                     P=0.500N        P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  17
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      8.3%            5.6%            2.2%          |      2.0%            2.3%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       1/18 (6%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         630           |      404             581             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.446N        P=0.601N        P=0.559N       |     P=0.335N        P=0.753         P=0.504N       |
|INCIDENTAL TUMOR       |     P=0.450N        P=0.601N        P=0.566N       |     P=0.500N        P=0.750         P=0.500N       |
|LOGISTIC REGRESSION    |     P=0.385N        P=0.601N        P=0.500N       |     P=0.268N        P=0.745         P=0.323N       |
|COCHRAN-ARMITAGE       |     P=0.378N                                       |     P=0.331N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       2/50 (4%)       4/50 (8%)      |     3/50 (6%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |     11.2%           11.1%           14.1%          |      9.3%            2.3%            3.1%          |
|TERMINAL (d)           |     2/24 (8%)       2/18 (11%)      1/18 (6%)      |     2/27 (7%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      693             729 (T)         581           |      404             581             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.323         P=0.620N        P=0.409        |     P=0.177N        P=0.269N        P=0.264N       |
|INCIDENTAL TUMOR       |     P=0.376         P=0.599N        P=0.489        |     P=0.245N        P=0.272N        P=0.262N       |
|LOGISTIC REGRESSION    |     P=0.415         P=0.558N        P=0.501        |     P=0.215N        P=0.311N        P=0.324N       |
|COCHRAN-ARMITAGE       |     P=0.417                                        |     P=0.202N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.500        |                     P=0.309N        P=0.309N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  18
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      8.3%            5.6%            2.2%          |      5.6%            2.3%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       1/18 (6%)       0/18 (0%)      |     1/27 (4%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         630           |      404             581             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.446N        P=0.601N        P=0.559N       |     P=0.135N        P=0.478N        P=0.223N       |
|INCIDENTAL TUMOR       |     P=0.450N        P=0.601N        P=0.566N       |     P=0.203N        P=0.487N        P=0.221N       |
|LOGISTIC REGRESSION    |     P=0.385N        P=0.601N        P=0.500N       |     P=0.134N        P=0.518N        P=0.231N       |
|COCHRAN-ARMITAGE       |     P=0.378N                                       |     P=0.142N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.500N        P=0.247N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    46/50 (92%)     48/50 (96%)     43/50 (86%)     |                                                    |
|ADJUSTED (b)           |    100.0%          100.0%           93.0%          |                                                    |
|TERMINAL (d)           |    24/24 (100%)    18/18 (100%)    15/18 (83%)     |                                                    |
|FIRST INCIDENCE (DAYS) |      538             495             534           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.322         P=0.099         P=0.352        |                                                    |
|INCIDENTAL TUMOR       |     P=0.118N        P=0.343         P=0.199N       |                                                    |
|LOGISTIC REGRESSION    |     P=0.138N        P=0.332         P=0.212N       |                                                    |
|COCHRAN-ARMITAGE       |     P=0.187N                                       |                                                    |
|FISHER EXACT           |                     P=0.339         P=0.262N       |                                                    |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  19
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       2/50 (4%)       3/50 (6%)      |     8/50 (16%)      6/50 (12%)      9/50 (18%)     |
|ADJUSTED (b)           |     15.7%            7.8%           11.6%          |     25.4%           16.4%           28.1%          |
|TERMINAL (d)           |     3/24 (13%)      0/18 (0%)       1/18 (6%)      |     5/27 (19%)      5/35 (14%)      9/32 (28%)     |
|FIRST INCIDENCE (DAYS) |      710             637             678           |      630             685             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.506N        P=0.441N        P=0.606N       |     P=0.538N        P=0.241N        P=0.569N       |
|INCIDENTAL TUMOR       |     P=0.401N        P=0.364N        P=0.505N       |     P=0.513         P=0.409N        P=0.557        |
|LOGISTIC REGRESSION    |     P=0.429N        P=0.372N        P=0.525N       |     P=0.553N        P=0.344N        P=0.587N       |
|COCHRAN-ARMITAGE       |     P=0.417N                                       |     P=0.445                                        |
|FISHER EXACT           |                     P=0.339N        P=0.500N       |                     P=0.387N        P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       2/50 (4%)      |     2/50 (4%)       4/50 (8%)       1/50 (2%)      |
|ADJUSTED (b)           |      4.2%            7.8%            5.1%          |      5.4%           11.4%            3.1%          |
|TERMINAL (d)           |     1/24 (4%)       1/18 (6%)       0/18 (0%)      |     0/27 (0%)       4/35 (11%)      1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         625             647           |      582             729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.357         P=0.434         P=0.470        |     P=0.344N        P=0.427         P=0.456N       |
|INCIDENTAL TUMOR       |     P=0.402         P=0.480         P=0.551        |     P=0.442N        P=0.309         P=0.656N       |
|LOGISTIC REGRESSION    |     P=0.389         P=0.491         P=0.499        |     P=0.383N        P=0.346         P=0.510N       |
|COCHRAN-ARMITAGE       |     P=0.390                                        |     P=0.406N                                       |
|FISHER EXACT           |                     P=0.500         P=0.500        |                     P=0.339         P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  20
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      4/50 (8%)       5/50 (10%)     |    10/50 (20%)     10/50 (20%)     10/50 (20%)     |
|ADJUSTED (b)           |     19.8%           15.0%           16.1%          |     29.5%           27.6%           31.3%          |
|TERMINAL (d)           |     4/24 (17%)      1/18 (6%)       1/18 (6%)      |     5/27 (19%)      9/35 (26%)     10/32 (31%)     |
|FIRST INCIDENCE (DAYS) |      710             625             647           |      582             685             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.472         P=0.626N        P=0.523        |     P=0.399N        P=0.400N        P=0.446N       |
|INCIDENTAL TUMOR       |     P=0.547N        P=0.535N        P=0.609N       |     P=0.509N        P=0.563         P=0.592        |
|LOGISTIC REGRESSION    |     P=0.566         P=0.536N        P=0.623        |     P=0.439N        P=0.563N        P=0.509N       |
|COCHRAN-ARMITAGE       |     P=0.568                                        |     P=0.550                                        |
|FISHER EXACT           |                     P=0.500N        P=0.630N       |                     P=0.598N        P=0.598N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%            7.7%          |      2.8%            0.0%            3.1%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       1/18 (6%)      |     0/27 (0%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             634           |      686             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.090           (e)           P=0.213        |     P=0.639N        P=0.484N        P=0.727N       |
|INCIDENTAL TUMOR       |     P=0.077           (e)           P=0.208        |     P=0.634N        P=0.674N        P=0.732N       |
|LOGISTIC REGRESSION    |     P=0.095           (e)           P=0.237        |     P=0.657N        P=0.500N        P=0.752N       |
|COCHRAN-ARMITAGE       |     P=0.095                                        |     P=0.669N                                       |
|FISHER EXACT           |                       (e)           P=0.247        |                     P=0.500N        P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  21
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     1/50 (2%)       2/50 (4%)       1/50 (2%)      |
|ADJUSTED (b)           |                                                    |      2.8%            5.7%            2.9%          |
|TERMINAL (d)           |                                                    |     0/27 (0%)       2/35 (6%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      686             729 (T)         727           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.572N        P=0.569         P=0.724N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.577N        P=0.463         P=0.747N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.587N        P=0.518         P=0.753N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.622N                                       |
|FISHER EXACT           |                                                    |                     P=0.500         P=0.753N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)     18/50 (36%)     13/50 (26%)     |
|ADJUSTED (b)           |                                                    |     28.3%           44.0%           34.4%          |
|TERMINAL (d)           |                                                    |     5/27 (19%)     13/35 (37%)      9/32 (28%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      404             481             517           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.440         P=0.170         P=0.471        |
|INCIDENTAL TUMOR       |                                                    |     P=0.212         P=0.077         P=0.235        |
|LOGISTIC REGRESSION    |                                                    |     P=0.266         P=0.057         P=0.291        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.287                                        |
|FISHER EXACT           |                                                    |                     P=0.059         P=0.318        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  22
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)     18/50 (36%)     14/50 (28%)     |
|ADJUSTED (b)           |                                                    |     28.3%           44.0%           36.1%          |
|TERMINAL (d)           |                                                    |     5/27 (19%)     13/35 (37%)      9/32 (28%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      404             481             517           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.365         P=0.170         P=0.396        |
|INCIDENTAL TUMOR       |                                                    |     P=0.157         P=0.077         P=0.174        |
|LOGISTIC REGRESSION    |                                                    |     P=0.200         P=0.057         P=0.219        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.218                                        |
|FISHER EXACT           |                                                    |                     P=0.059         P=0.241        |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      4.6%            3.2%            2.3%          |      0.0%            2.4%            2.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      581             681             637           |      ---             608             407           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.374N        P=0.521N        P=0.486N       |     P=0.341         P=0.490         P=0.500        |
|INCIDENTAL TUMOR       |     P=0.315N        P=0.439N        P=0.458N       |     P=0.157         P=0.388         P=0.500        |
|LOGISTIC REGRESSION    |     P=0.423N        P=0.512N        P=0.568N       |     P=0.361         P=0.492         P=0.663        |
|COCHRAN-ARMITAGE       |     P=0.378N                                       |     P=0.331                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.500         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  23
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    27/50 (54%)     28/50 (56%)     25/50 (50%)     |    14/50 (28%)     12/50 (24%)     11/50 (22%)     |
|ADJUSTED (b)           |     64.1%           71.1%           68.7%          |     34.1%           26.7%           26.0%          |
|TERMINAL (d)           |    10/24 (42%)      8/18 (44%)      9/18 (50%)     |     3/27 (11%)      4/35 (11%)      4/32 (13%)     |
|FIRST INCIDENCE (DAYS) |      538             535             534           |      582             481             517           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.445         P=0.274         P=0.478        |     P=0.201N        P=0.325N        P=0.221N       |
|INCIDENTAL TUMOR       |     P=0.285N        P=0.525N        P=0.338N       |     P=0.548N        P=0.386         P=0.551        |
|LOGISTIC REGRESSION    |     P=0.387N        P=0.558         P=0.428N       |     P=0.444         P=0.565         P=0.490        |
|COCHRAN-ARMITAGE       |     P=0.382N                                       |     P=0.281N                                       |
|FISHER EXACT           |                     P=0.500         P=0.421N       |                     P=0.410N        P=0.322N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%            4.2%            5.6%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       0/32 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         710             651           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.349         P=0.715         P=0.466        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.445         P=0.736         P=0.551        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.379         P=0.738         P=0.501        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.378                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.753N        P=0.500        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  24
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      7.5%            0.0%            0.0%          |      0.0%            0.0%            5.8%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      283             ---             ---           |      ---             ---             724           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.041N*       P=0.133N        P=0.130N       |     P=0.112           (e)           P=0.287        |
|INCIDENTAL TUMOR       |     P=0.065N        P=0.223N        P=0.161N       |     P=0.121           (e)           P=0.268        |
|LOGISTIC REGRESSION    |     P=0.061N        P=0.146N        P=0.196N       |     P=0.112           (e)           P=0.280        |
|COCHRAN-ARMITAGE       |     P=0.037N*                                      |     P=0.095                                        |
|FISHER EXACT           |                     P=0.121N        P=0.121N       |                       (e)           P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      7.5%            0.0%            0.0%          |      0.0%            0.0%            5.8%          |
|TERMINAL (d)           |     0/24 (0%)       0/18 (0%)       0/18 (0%)      |     0/27 (0%)       0/35 (0%)       1/32 (3%)      |
|FIRST INCIDENCE (DAYS) |      283             ---             ---           |      ---             ---             724           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.041N*       P=0.133N        P=0.130N       |     P=0.112           (e)           P=0.287        |
|INCIDENTAL TUMOR       |     P=0.065N        P=0.223N        P=0.161N       |     P=0.121           (e)           P=0.268        |
|LOGISTIC REGRESSION    |     P=0.061N        P=0.146N        P=0.196N       |     P=0.112           (e)           P=0.280        |
|COCHRAN-ARMITAGE       |     P=0.037N*                                      |     P=0.095                                        |
|FISHER EXACT           |                     P=0.121N        P=0.121N       |                       (e)           P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  25
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    47/50 (94%)     50/50 (100%)    50/50 (100%)    |    44/50 (88%)     44/50 (88%)     42/50 (84%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     91.6%           93.6%           91.2%          |
|TERMINAL (d)           |    24/24 (100%)    18/18 (100%)    18/18 (100%)    |    23/27 (85%)     32/35 (91%)     28/32 (88%)     |
|FIRST INCIDENCE (DAYS) |      538             495             534           |      404             481             517           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.099         P=0.082         P=0.101        |     P=0.104N        P=0.134N        P=0.119N       |
|INCIDENTAL TUMOR       |     P=0.073         P=0.190         P=0.200        |     P=0.189N        P=0.608N        P=0.303N       |
|LOGISTIC REGRESSION    |     P=0.066         P=0.138         P=0.214        |     P=0.286N        P=0.615N        P=0.340N       |
|COCHRAN-ARMITAGE       |     P=0.037 *                                      |     P=0.330N                                       |
|FISHER EXACT           |                     P=0.121         P=0.121        |                     P=0.620N        P=0.387N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    36/50 (72%)     35/50 (70%)     33/50 (66%)     |    21/50 (42%)     20/50 (40%)     20/50 (40%)     |
|ADJUSTED (b)           |     77.6%           78.7%           75.7%          |     47.7%           42.6%           44.3%          |
|TERMINAL (d)           |    14/24 (58%)      9/18 (50%)      9/18 (50%)     |     6/27 (22%)      9/35 (26%)      8/32 (25%)     |
|FIRST INCIDENCE (DAYS) |      283             496             534           |      404             481             407           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.463         P=0.335         P=0.491        |     P=0.305N        P=0.352N        P=0.317N       |
|INCIDENTAL TUMOR       |     P=0.197N        P=0.385N        P=0.244N       |     P=0.356         P=0.336         P=0.440        |
|LOGISTIC REGRESSION    |     P=0.278N        P=0.459N        P=0.294N       |     P=0.317         P=0.549N        P=0.377        |
|COCHRAN-ARMITAGE       |     P=0.294N                                       |     P=0.459N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.333N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/08/94                     EXPERIMENT: 05058 TEST: 01                                                 PAGE  26
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- ROXARSONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.005%          0.01%         |      UNTREATD        0.005%          0.01%         |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    50/50 (100%)    50/50 (100%)    50/50 (100%)    |    48/50 (96%)     47/50 (94%)     46/50 (92%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     96.0%           94.0%           93.9%          |
|TERMINAL (d)           |    24/24 (100%)    18/18 (100%)    18/18 (100%)    |    25/27 (93%)     32/35 (91%)     29/32 (91%)     |
|FIRST INCIDENCE (DAYS) |      283             495             534           |      404             481             407           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.189         P=0.166         P=0.199        |     P=0.103N        P=0.106N        P=0.109N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.319N        P=0.618N        P=0.404N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.265N        P=0.618N        P=0.320N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.264N                                       |
|FISHER EXACT           |                     P=1.000N        P=1.000N       |                     P=0.500N        P=0.339N       |
|=================================================================================================================================|
 
 (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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