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TDMS Study 05091-02 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: American Biogenics                                     DIHYDROCOUMARIN                                    DATE: 09/12/94       
EXPERIMENT: 05091 TEST: 02                                                                                     TIME: 13:18:28       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-45039          ROUTE: GAVAGE                                                                      NTP C#: 55890B       
PATHOLOGIST: R. DAHLGREN                     S. EUSTIS                                                         CAS: 119-84-6        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: American Biogenics                                     DIHYDROCOUMARIN                                    DATE: 09/12/94      
EXPERIMENT: 05091 TEST: 02                                                                                     TIME: 13:18:28      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NO1-ES-45039          ROUTE: GAVAGE                                                                      NTP C#: 55890B      
PATHOLOGIST: R. DAHLGREN                     S. EUSTIS                                                         CAS: 119-84-6       
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: American Biogenics                                     DIHYDROCOUMARIN                                    DATE: 09/12/94       
EXPERIMENT: 05091 TEST: 02                                                                                     TIME: 13:18:28       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-45039          ROUTE: GAVAGE                                                                      NTP C#: 55890B       
PATHOLOGIST: R. DAHLGREN                     S. EUSTIS                                                         CAS: 119-84-6        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                        IN THE ANALYSIS OF THE STUDY OF DIHYDROCOUMARIN
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Intestine Small               Carcinoma or Adenoma
                             Liver                         Hepatoblastoma
                                                           Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             All Organs                    Malignant Lymphoma And Histiocytic Sarcoma
                                                           Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,
                                                            NOS, or Undifferentiated Cell Type
                                                           Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hemangiosarcoma
                                                           Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                             Spleen                        Hemangiosarcoma
                             All Organs                    Hemangiosarcoma
                                                           Hemangiosarcoma or Hemangioma
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   1
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/60 (8%)    4/58 (7%)    2/56 (4%)    2/60 (3%)  |  1/60 (2%)    3/56 (5%)    3/58 (5%)    1/61 (2%)  |
|ADJUSTED (b)           |  11.9%         9.3%         5.4%         5.1%      |   2.4%         7.2%         7.3%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/7 (14%)    0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  5/42 (12%)   2/39 (5%)    1/34 (3%)    1/38 (3%)  |  0/36 (0%)    2/39 (5%)    3/41 (7%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      456 (I)      675          722       |   674          671          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.168N     P=0.561N     P=0.303N     P=0.259N   |  P=0.589N     P=0.337      P=0.353      P=0.718    |
|INCIDENTAL TUMOR       |  P=0.133N     P=0.540N     P=0.234N     P=0.236N   |  P=0.535N     P=0.318      P=0.342      P=0.754N   |
|LOGISTIC REGRESSION    |  P=0.142N     P=0.519N     P=0.247N     P=0.246N   |  P=0.556N     P=0.314      P=0.332      P=0.742    |
|COCHRAN-ARMITAGE       |  P=0.135N                                          |  P=0.485N                                          |
|FISHER EXACT           |               P=0.522N     P=0.249N     P=0.219N   |               P=0.284      P=0.297      P=0.748N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/60 (8%)    5/58 (9%)    2/56 (4%)    2/60 (3%)  |  1/60 (2%)    3/56 (5%)    3/58 (5%)    1/61 (2%)  |
|ADJUSTED (b)           |  11.9%        10.9%         5.4%         5.1%      |   2.4%         7.2%         7.3%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/7 (14%)    0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  5/42 (12%)   2/39 (5%)    1/34 (3%)    1/38 (3%)  |  0/36 (0%)    2/39 (5%)    3/41 (7%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      438          675          722       |   674          671          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.145N     P=0.568      P=0.303N     P=0.259N   |  P=0.589N     P=0.337      P=0.353      P=0.718    |
|INCIDENTAL TUMOR       |  P=0.104N     P=0.591      P=0.234N     P=0.236N   |  P=0.535N     P=0.318      P=0.342      P=0.754N   |
|LOGISTIC REGRESSION    |  P=0.117N     P=0.610      P=0.247N     P=0.246N   |  P=0.556N     P=0.314      P=0.332      P=0.742    |
|COCHRAN-ARMITAGE       |  P=0.114N                                          |  P=0.485N                                          |
|FISHER EXACT           |               P=0.607      P=0.249N     P=0.219N   |               P=0.284      P=0.297      P=0.748N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   2
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    0/58 (0%)    1/56 (2%)    0/60 (0%)  |  0/60 (0%)    0/56 (0%)    0/58 (0%)    0/61 (0%)  |
|ADJUSTED (b)           |   9.3%         0.0%         2.9%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/42 (7%)    0/39 (0%)    1/34 (3%)    0/38 (0%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   690          ---          729 (T)      ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.050N*    P=0.075N     P=0.246N     P=0.078N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.040N*    P=0.062N     P=0.171N     P=0.065N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.044N*    P=0.067N     P=0.202N     P=0.070N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.041N*                                         |    (e)                                             |
|FISHER EXACT           |               P=0.064N     P=0.204N     P=0.059N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/58 (0%)    0/56 (0%)    0/60 (0%)  |  0/60 (0%)    0/56 (0%)    0/58 (0%)    0/61 (0%)  |
|ADJUSTED (b)           |   4.8%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/42 (5%)    0/39 (0%)    0/34 (0%)    0/38 (0%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.130N     P=0.255N     P=0.286N     P=0.261N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.130N     P=0.255N     P=0.286N     P=0.261N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.130N     P=0.255N     P=0.286N     P=0.261N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.117N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.256N     P=0.265N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   3
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    2/57 (4%)    0/54 (0%)    0/60 (0%)  |  0/59 (0%)    1/56 (2%)    0/56 (0%)    0/56 (0%)  |
|ADJUSTED (b)           |   0.0%         5.1%         0.0%         0.0%      |   0.0%         2.6%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    2/39 (5%)    0/34 (0%)    0/38 (0%)  |  0/36 (0%)    1/39 (3%)    0/41 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.428N     P=0.222        (e)          (e)      |  P=0.609N     P=0.516        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.428N     P=0.222        (e)          (e)      |  P=0.609N     P=0.516        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.428N     P=0.222        (e)          (e)      |  P=0.609N     P=0.516        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.403N                                          |  P=0.573N                                          |
|FISHER EXACT           |               P=0.239        (e)          (e)      |               P=0.487        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/58 (0%)    2/56 (4%)    0/59 (0%)  |  0/57 (0%)    0/56 (0%)    0/56 (0%)    0/56 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         5.9%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/39 (0%)    2/34 (6%)    0/38 (0%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.572        (e)        P=0.193        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.572        (e)        P=0.193        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.572        (e)        P=0.193        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.591                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.231        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   4
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/58 (2%)    2/56 (4%)    1/59 (2%)  |  0/57 (0%)    0/56 (0%)    0/56 (0%)    0/56 (0%)  |
|ADJUSTED (b)           |   0.0%         2.6%         5.9%         2.6%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/39 (3%)    2/34 (6%)    1/38 (3%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      729 (T)      729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.340      P=0.485      P=0.193      P=0.480    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.340      P=0.485      P=0.193      P=0.480    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.340      P=0.485      P=0.193      P=0.480    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.364                                           |    (e)                                             |
|FISHER EXACT           |               P=0.492      P=0.231      P=0.496    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/58 (0%)    0/56 (0%)    0/60 (0%)  |  0/60 (0%)    0/56 (0%)    0/58 (0%)    2/61 (3%)  |
|ADJUSTED (b)           |   4.2%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         6.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    0/39 (0%)    0/34 (0%)    0/38 (0%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   456          ---          ---          ---       |   ---          ---          ---          703       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.125N     P=0.256N     P=0.272N     P=0.253N   |  P=0.030 *      (e)          (e)        P=0.198    |
|INCIDENTAL TUMOR       |  P=0.106N     P=0.248N     P=0.309N     P=0.194N   |  P=0.049 *      (e)          (e)        P=0.246    |
|LOGISTIC REGRESSION    |  P=0.120N     P=0.249N     P=0.258N     P=0.244N   |  P=0.034 *      (e)          (e)        P=0.207    |
|COCHRAN-ARMITAGE       |  P=0.117N                                          |  P=0.051                                           |
|FISHER EXACT           |               P=0.256N     P=0.265N     P=0.248N   |                 (e)          (e)        P=0.252    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   5
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatoblastoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/58 (0%)    0/56 (0%)    2/60 (3%)  |  0/60 (0%)    0/56 (0%)    0/58 (0%)    0/61 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         5.3%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/39 (0%)    0/34 (0%)    2/38 (5%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.044 *      (e)          (e)        P=0.217    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.044 *      (e)          (e)        P=0.217    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.044 *      (e)          (e)        P=0.217    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.049 *                                         |    (e)                                             |
|FISHER EXACT           |                 (e)          (e)        P=0.248    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/60 (53%)  27/58 (47%)  38/56 (68%)  34/60 (57%) | 12/60 (20%)  20/56 (36%)  24/58 (41%)  22/61 (36%) |
|ADJUSTED (b)           |  65.9%        58.1%        82.3%        73.3%      |  30.4%        45.2%        54.1%        57.5%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   4/7 (57%)    2/5 (40%)    3/10 (30%) |  2/9 (22%)    0/6 (0%)     2/8 (25%)    2/9 (22%)  |
|TERMINAL (d)           | 26/42 (62%)  20/39 (51%)  26/34 (76%)  26/38 (68%) | 10/36 (28%)  15/39 (38%)  21/41 (51%)  14/29 (48%) |
|FIRST INCIDENCE (DAYS) |   449          455 (I)      455 (I)      438       |   455 (I)      594          455 (I)      420       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.114      P=0.431N     P=0.014 *    P=0.252    |  P=0.005 **   P=0.103      P=0.028 *    P=0.008 ** |
|INCIDENTAL TUMOR       |  P=0.204      P=0.325N     P=0.074      P=0.408    |  P=0.014 *    P=0.085      P=0.027 *    P=0.016 *  |
|LOGISTIC REGRESSION    |  P=0.204      P=0.281N     P=0.087      P=0.405    |  P=0.021 *    P=0.084      P=0.017 *    P=0.024 *  |
|COCHRAN-ARMITAGE       |  P=0.228                                           |  P=0.059                                           |
|FISHER EXACT           |               P=0.290N     P=0.079      P=0.427    |               P=0.046 *    P=0.010 **   P=0.038 *  |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   6
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/60 (18%)  11/58 (19%)  11/56 (20%)   6/60 (10%) |  3/60 (5%)    2/56 (4%)    4/58 (7%)    6/61 (10%) |
|ADJUSTED (b)           |  24.3%        23.1%        25.5%        13.4%      |   7.7%         4.8%         8.9%        15.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/42 (19%)   4/39 (10%)   4/34 (12%)   2/38 (5%)  |  1/36 (3%)    1/39 (3%)    3/41 (7%)    2/29 (7%)  |
|FIRST INCIDENCE (DAYS) |   591          423          583          477       |   674          685          444          504       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.171N     P=0.537      P=0.450      P=0.202N   |  P=0.068      P=0.455N     P=0.559      P=0.178    |
|INCIDENTAL TUMOR       |  P=0.033N*    P=0.280N     P=0.183N     P=0.069N   |  P=0.292      P=0.485N     P=0.618      P=0.456    |
|LOGISTIC REGRESSION    |  P=0.037N*    P=0.490N     P=0.238N     P=0.065N   |  P=0.154      P=0.484N     P=0.503      P=0.275    |
|COCHRAN-ARMITAGE       |  P=0.113N                                          |  P=0.125                                           |
|FISHER EXACT           |               P=0.558      P=0.522      P=0.148N   |               P=0.533N     P=0.481      P=0.254    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/60 (18%)  11/58 (19%)  11/56 (20%)   7/60 (12%) |  3/60 (5%)    2/56 (4%)    4/58 (7%)    6/61 (10%) |
|ADJUSTED (b)           |  24.3%        23.1%        25.5%        15.8%      |   7.7%         4.8%         8.9%        15.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/42 (19%)   4/39 (10%)   4/34 (12%)   3/38 (8%)  |  1/36 (3%)    1/39 (3%)    3/41 (7%)    2/29 (7%)  |
|FIRST INCIDENCE (DAYS) |   591          423          583          477       |   674          685          444          504       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.246N     P=0.537      P=0.450      P=0.289N   |  P=0.068      P=0.455N     P=0.559      P=0.178    |
|INCIDENTAL TUMOR       |  P=0.066N     P=0.280N     P=0.183N     P=0.122N   |  P=0.292      P=0.485N     P=0.618      P=0.456    |
|LOGISTIC REGRESSION    |  P=0.072N     P=0.490N     P=0.238N     P=0.119N   |  P=0.154      P=0.484N     P=0.503      P=0.275    |
|COCHRAN-ARMITAGE       |  P=0.174N                                          |  P=0.125                                           |
|FISHER EXACT           |               P=0.558      P=0.522      P=0.222N   |               P=0.533N     P=0.481      P=0.254    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   7
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 39/60 (65%)  34/58 (59%)  42/56 (75%)  36/60 (60%) | 15/60 (25%)  21/56 (38%)  27/58 (47%)  26/61 (43%) |
|ADJUSTED (b)           |  76.1%        66.4%        84.0%        74.5%      |  36.5%        46.5%        59.4%        61.6%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   4/7 (57%)    2/5 (40%)    3/10 (30%) |  2/9 (22%)    0/6 (0%)     2/8 (25%)    2/9 (22%)  |
|TERMINAL (d)           | 30/42 (71%)  22/39 (56%)  26/34 (76%)  26/38 (68%) | 11/36 (31%)  15/39 (38%)  23/41 (56%)  14/29 (48%) |
|FIRST INCIDENCE (DAYS) |   449          423          455 (I)      438       |   455 (I)      594          444          420       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.400      P=0.460N     P=0.049 *    P=0.563    |  P=0.003 **   P=0.225      P=0.043 *    P=0.008 ** |
|INCIDENTAL TUMOR       |  P=0.375N     P=0.187N     P=0.445      P=0.292N   |  P=0.019 *    P=0.176      P=0.046 *    P=0.031 *  |
|LOGISTIC REGRESSION    |  P=0.384N     P=0.289N     P=0.288      P=0.365N   |  P=0.013 *    P=0.179      P=0.021 *    P=0.021 *  |
|COCHRAN-ARMITAGE       |  P=0.443N                                          |  P=0.033 *                                         |
|FISHER EXACT           |               P=0.300N     P=0.166      P=0.353N   |               P=0.105      P=0.012 *    P=0.031 *  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 39/60 (65%)  34/58 (59%)  42/56 (75%)  37/60 (62%) | 15/60 (25%)  21/56 (38%)  27/58 (47%)  26/61 (43%) |
|ADJUSTED (b)           |  76.1%        66.4%        84.0%        76.6%      |  36.5%        46.5%        59.4%        61.6%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   4/7 (57%)    2/5 (40%)    3/10 (30%) |  2/9 (22%)    0/6 (0%)     2/8 (25%)    2/9 (22%)  |
|TERMINAL (d)           | 30/42 (71%)  22/39 (56%)  26/34 (76%)  27/38 (71%) | 11/36 (31%)  15/39 (38%)  23/41 (56%)  14/29 (48%) |
|FIRST INCIDENCE (DAYS) |   449          423          455 (I)      438       |   455 (I)      594          444          420       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.334      P=0.460N     P=0.049 *    P=0.491    |  P=0.003 **   P=0.225      P=0.043 *    P=0.008 ** |
|INCIDENTAL TUMOR       |  P=0.459N     P=0.187N     P=0.445      P=0.366N   |  P=0.019 *    P=0.176      P=0.046 *    P=0.031 *  |
|LOGISTIC REGRESSION    |  P=0.470N     P=0.289N     P=0.288      P=0.441N   |  P=0.013 *    P=0.179      P=0.021 *    P=0.021 *  |
|COCHRAN-ARMITAGE       |  P=0.525N                                          |  P=0.033 *                                         |
|FISHER EXACT           |               P=0.300N     P=0.166      P=0.425N   |               P=0.105      P=0.012 *    P=0.031 *  |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   8
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  9/60 (15%)  16/57 (28%)  17/56 (30%)  11/60 (18%) |  2/60 (3%)    5/56 (9%)    1/56 (2%)    3/60 (5%)  |
|ADJUSTED (b)           |  20.5%        39.6%        43.8%        26.9%      |   5.6%        12.3%         2.4%         9.5%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   1/7 (14%)    2/5 (40%)    1/10 (10%) |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/42 (19%)  15/39 (38%)  13/34 (38%)   9/38 (24%) |  2/36 (6%)    4/39 (10%)   1/41 (2%)    2/28 (7%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      455 (I)      455 (I)      456 (I)   |   729 (T)      671          729 (T)      595       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.385      P=0.047 *    P=0.010 **   P=0.322    |  P=0.489      P=0.252      P=0.455N     P=0.395    |
|INCIDENTAL TUMOR       |  P=0.415      P=0.047 *    P=0.016 *    P=0.369    |  P=0.517      P=0.246      P=0.455N     P=0.409    |
|LOGISTIC REGRESSION    |  P=0.468      P=0.065      P=0.041 *    P=0.378    |  P=0.534      P=0.247      P=0.455N     P=0.444    |
|COCHRAN-ARMITAGE       |  P=0.501                                           |  P=0.554N                                          |
|FISHER EXACT           |               P=0.067      P=0.039 *    P=0.404    |               P=0.192      P=0.526N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    3/57 (5%)    1/56 (2%)    3/60 (5%)  |  0/60 (0%)    1/56 (2%)    0/56 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   2.3%         7.2%         2.6%         7.2%      |   0.0%         2.1%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/39 (3%)    0/34 (0%)    2/38 (5%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   690          643          715          477       |   ---          615          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.289      P=0.290      P=0.733      P=0.284    |  P=0.593N     P=0.513        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.398      P=0.404      P=0.530N     P=0.360    |  P=0.565N     P=0.455        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.315      P=0.289      P=0.750      P=0.305    |  P=0.558N     P=0.463        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.319                                           |  P=0.564N                                          |
|FISHER EXACT           |               P=0.290      P=0.735      P=0.309    |               P=0.483        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE   9
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/60 (17%)  19/57 (33%)  18/56 (32%)  14/60 (23%) |  2/60 (3%)    6/56 (11%)   1/56 (2%)    3/60 (5%)  |
|ADJUSTED (b)           |  22.4%        44.9%        45.2%        33.3%      |   5.6%        14.1%         2.4%         9.5%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   1/7 (14%)    2/5 (40%)    1/10 (10%) |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/42 (19%)  16/39 (41%)  13/34 (38%)  11/38 (29%) |  2/36 (6%)    4/39 (10%)   1/41 (2%)    2/28 (7%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      455 (I)      455 (I)      456 (I)   |   729 (T)      615          729 (T)      595       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.274      P=0.023 *    P=0.012 *    P=0.182    |  P=0.546      P=0.165      P=0.455N     P=0.395    |
|INCIDENTAL TUMOR       |  P=0.342      P=0.030 *    P=0.029 *    P=0.243    |  P=0.573      P=0.148      P=0.455N     P=0.409    |
|LOGISTIC REGRESSION    |  P=0.353      P=0.028 *    P=0.044 *    P=0.229    |  P=0.560N     P=0.147      P=0.455N     P=0.444    |
|COCHRAN-ARMITAGE       |  P=0.386                                           |  P=0.492N                                          |
|FISHER EXACT           |               P=0.030 *    P=0.042 *    P=0.247    |               P=0.115      P=0.526N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/59 (2%)    2/56 (4%)    1/57 (2%)    0/59 (0%)  |
|ADJUSTED (b)           |                                                    |   2.8%         5.1%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  1/36 (3%)    2/39 (5%)    1/41 (2%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.295N     P=0.528      P=0.733N     P=0.550N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.295N     P=0.528      P=0.733N     P=0.550N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.294N     P=0.528      P=0.733N     P=0.550N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.246N                                          |
|FISHER EXACT           |                                                    |               P=0.480      P=0.743      P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  10
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/57 (0%)    0/53 (0%)    1/50 (2%)    1/55 (2%)  |  9/56 (16%)   5/54 (9%)    3/55 (5%)    3/56 (5%)  |
|ADJUSTED (b)           |   0.0%         0.0%         3.1%         2.2%      |  26.2%        12.4%         7.3%         9.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/40 (0%)    0/37 (0%)    1/32 (3%)    0/36 (0%)  |  8/33 (24%)   3/37 (8%)    3/41 (7%)    2/28 (7%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      561       |   704          703          729 (T)      646       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.228        (e)        P=0.455      P=0.496    |  P=0.061N     P=0.139N     P=0.026N*    P=0.108N   |
|INCIDENTAL TUMOR       |  P=0.265        (e)        P=0.455      P=0.718    |  P=0.057N     P=0.146N     P=0.034N*    P=0.096N   |
|LOGISTIC REGRESSION    |  P=0.234        (e)        P=0.455      P=0.471    |  P=0.057N     P=0.126N     P=0.027N*    P=0.097N   |
|COCHRAN-ARMITAGE       |  P=0.235                                           |  P=0.040N*                                         |
|FISHER EXACT           |                 (e)        P=0.467      P=0.491    |               P=0.217N     P=0.066N     P=0.062N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    0/57 (0%)    1/51 (2%)    2/58 (3%)  |  0/60 (0%)    0/56 (0%)    0/57 (0%)    2/55 (4%)  |
|ADJUSTED (b)           |   2.4%         0.0%         2.9%         4.0%      |   0.0%         0.0%         0.0%         5.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/42 (2%)    0/39 (0%)    1/34 (3%)    0/38 (0%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    1/28 (4%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          729 (T)      417       |   ---          ---          ---          583       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.237      P=0.515N     P=0.714      P=0.482    |  P=0.031 *      (e)          (e)        P=0.198    |
|INCIDENTAL TUMOR       |  P=0.268      P=0.515N     P=0.714      P=0.546    |  P=0.028 *      (e)          (e)        P=0.161    |
|LOGISTIC REGRESSION    |  P=0.245      P=0.515N     P=0.714      P=0.486    |  P=0.042 *      (e)          (e)        P=0.214    |
|COCHRAN-ARMITAGE       |  P=0.246                                           |  P=0.043 *                                         |
|FISHER EXACT           |               P=0.509N     P=0.715      P=0.494    |                 (e)          (e)        P=0.227    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  11
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    1/58 (2%)    0/56 (0%)    2/60 (3%)  |  0/60 (0%)    0/56 (0%)    0/58 (0%)    0/61 (0%)  |
|ADJUSTED (b)           |   2.1%         2.6%         0.0%         5.1%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    1/39 (3%)    0/34 (0%)    1/38 (3%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   528          729 (T)      ---          722       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.346      P=0.752      P=0.496N     P=0.475    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.414      P=0.752      P=0.581N     P=0.580    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.367      P=0.753      P=0.521N     P=0.500    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.369                                           |    (e)                                             |
|FISHER EXACT           |               P=0.744      P=0.517N     P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    1/58 (2%)    5/56 (9%)    4/60 (7%)  |  2/60 (3%)    2/56 (4%)    1/58 (2%)    1/61 (2%)  |
|ADJUSTED (b)           |   6.8%         2.6%        14.7%        10.3%      |   5.6%         5.1%         2.4%         2.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/42 (5%)    1/39 (3%)    5/34 (15%)   3/38 (8%)  |  2/36 (6%)    2/39 (5%)    1/41 (2%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   528          729 (T)      729 (T)      722       |   729 (T)      729 (T)      729 (T)      529       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.226      P=0.327N     P=0.262      P=0.453    |  P=0.397N     P=0.666N     P=0.455N     P=0.557N   |
|INCIDENTAL TUMOR       |  P=0.258      P=0.327N     P=0.237      P=0.522    |  P=0.251N     P=0.666N     P=0.455N     P=0.350N   |
|LOGISTIC REGRESSION    |  P=0.246      P=0.316N     P=0.327      P=0.485    |  P=0.354N     P=0.666N     P=0.454N     P=0.505N   |
|COCHRAN-ARMITAGE       |  P=0.269                                           |  P=0.327N                                          |
|FISHER EXACT           |               P=0.322N     P=0.320      P=0.500    |               P=0.664      P=0.513N     P=0.494N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  12
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/58 (0%)    5/56 (9%)    2/60 (3%)  |  2/60 (3%)    2/56 (4%)    1/58 (2%)    1/61 (2%)  |
|ADJUSTED (b)           |   4.8%         0.0%        14.7%         5.3%      |   5.6%         5.1%         2.4%         2.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/42 (5%)    0/39 (0%)    5/34 (15%)   2/38 (5%)  |  2/36 (6%)    2/39 (5%)    1/41 (2%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          729 (T)      729 (T)   |   729 (T)      729 (T)      729 (T)      529       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.344      P=0.255N     P=0.139      P=0.658    |  P=0.397N     P=0.666N     P=0.455N     P=0.557N   |
|INCIDENTAL TUMOR       |  P=0.344      P=0.255N     P=0.139      P=0.658    |  P=0.251N     P=0.666N     P=0.455N     P=0.350N   |
|LOGISTIC REGRESSION    |  P=0.344      P=0.255N     P=0.139      P=0.658    |  P=0.354N     P=0.666N     P=0.454N     P=0.505N   |
|COCHRAN-ARMITAGE       |  P=0.390                                           |  P=0.327N                                          |
|FISHER EXACT           |               P=0.256N     P=0.192      P=0.691N   |               P=0.664      P=0.513N     P=0.494N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    0/56 (0%)    0/54 (0%)    2/60 (3%)  |  0/57 (0%)    1/56 (2%)    1/57 (2%)    1/58 (2%)  |
|ADJUSTED (b)           |   1.9%         0.0%         0.0%         5.3%      |   0.0%         2.3%         2.4%         3.6%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/39 (0%)    0/33 (0%)    2/38 (5%)  |  0/36 (0%)    0/39 (0%)    1/41 (2%)    1/28 (4%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      ---          ---          729 (T)   |   ---          703          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.246      P=0.571N     P=0.638N     P=0.477    |  P=0.320      P=0.525      P=0.526      P=0.450    |
|INCIDENTAL TUMOR       |  P=0.246      P=0.571N     P=0.638N     P=0.477    |  P=0.379      P=0.536      P=0.526      P=0.450    |
|LOGISTIC REGRESSION    |  P=0.256      P=0.533N     P=0.619N     P=0.507    |  P=0.337      P=0.514      P=0.526      P=0.450    |
|COCHRAN-ARMITAGE       |  P=0.255                                           |  P=0.391                                           |
|FISHER EXACT           |               P=0.513N     P=0.522N     P=0.506    |               P=0.496      P=0.500      P=0.504    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  13
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/60 (0%)    2/56 (4%)    0/58 (0%)    0/61 (0%)  |
|ADJUSTED (b)           |                                                    |   0.0%         5.1%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  0/36 (0%)    2/39 (5%)    0/41 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.445N     P=0.256        (e)          (e)      |
|INCIDENTAL TUMOR       |                                                    |  P=0.445N     P=0.256        (e)          (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.445N     P=0.256        (e)          (e)      |
|COCHRAN-ARMITAGE       |                                                    |  P=0.399N                                          |
|FISHER EXACT           |                                                    |               P=0.231        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/60 (2%)    2/56 (4%)    0/58 (0%)    0/61 (0%)  |
|ADJUSTED (b)           |                                                    |   2.8%         5.1%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  1/36 (3%)    2/39 (5%)    0/41 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   729 (T)      729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.213N     P=0.528      P=0.474N     P=0.543N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.213N     P=0.528      P=0.474N     P=0.543N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.213N     P=0.528      P=0.474N     P=0.543N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.185N                                          |
|FISHER EXACT           |                                                    |               P=0.474      P=0.508N     P=0.496N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  14
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/58 (3%)    1/56 (2%)    1/60 (2%)  |  0/60 (0%)    0/56 (0%)    1/58 (2%)    0/61 (0%)  |
|ADJUSTED (b)           |   0.0%         5.1%         2.9%         1.7%      |   0.0%         0.0%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    2/39 (5%)    1/34 (3%)    0/38 (0%)  |  0/36 (0%)    0/39 (0%)    1/41 (2%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      729 (T)      417       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.478      P=0.222      P=0.458      P=0.503    |  P=0.676        (e)        P=0.526        (e)      |
|INCIDENTAL TUMOR       |  P=0.520      P=0.222      P=0.458      P=0.602    |  P=0.676        (e)        P=0.526        (e)      |
|LOGISTIC REGRESSION    |  P=0.501      P=0.222      P=0.458      P=0.407    |  P=0.676        (e)        P=0.526        (e)      |
|COCHRAN-ARMITAGE       |  P=0.501                                           |  P=0.697                                           |
|FISHER EXACT           |               P=0.239      P=0.483      P=0.500    |                 (e)        P=0.492        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    0/58 (0%)    1/56 (2%)    2/60 (3%)  |  0/60 (0%)    0/56 (0%)    0/58 (0%)    4/61 (7%)  |
|ADJUSTED (b)           |   6.5%         0.0%         2.9%         4.0%      |   0.0%         0.0%         0.0%        12.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/42 (5%)    0/39 (0%)    1/34 (3%)    0/38 (0%)  |  0/36 (0%)    0/39 (0%)    0/41 (0%)    2/29 (7%)  |
|FIRST INCIDENCE (DAYS) |   456          ---          729 (T)      417       |   ---          ---          ---          583       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.576N     P=0.137N     P=0.372N     P=0.524N   |  P=0.001 **     (e)          (e)        P=0.045 *  |
|INCIDENTAL TUMOR       |  P=0.486N     P=0.132N     P=0.403N     P=0.400N   |  P=0.004 **     (e)          (e)        P=0.060    |
|LOGISTIC REGRESSION    |  P=0.557N     P=0.128N     P=0.330N     P=0.512N   |  P=0.003 **     (e)          (e)        P=0.055    |
|COCHRAN-ARMITAGE       |  P=0.554N                                          |  P=0.004 **                                        |
|FISHER EXACT           |               P=0.128N     P=0.336N     P=0.500N   |                 (e)          (e)        P=0.061    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  15
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    2/58 (3%)    2/56 (4%)    2/60 (3%)  |  0/60 (0%)    0/56 (0%)    1/58 (2%)    4/61 (7%)  |
|ADJUSTED (b)           |   6.5%         5.1%         5.9%         4.0%      |   0.0%         0.0%         2.4%        12.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     0/5 (0%)     0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/42 (5%)    2/39 (5%)    2/34 (6%)    0/38 (0%)  |  0/36 (0%)    0/39 (0%)    1/41 (2%)    2/29 (7%)  |
|FIRST INCIDENCE (DAYS) |   456          729 (T)      729 (T)      417       |   ---          ---          729 (T)      583       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.466N     P=0.534N     P=0.583N     P=0.524N   |  P=0.002 **     (e)        P=0.526      P=0.045 *  |
|INCIDENTAL TUMOR       |  P=0.393N     P=0.527N     P=0.612N     P=0.400N   |  P=0.006 **     (e)        P=0.526      P=0.060    |
|LOGISTIC REGRESSION    |  P=0.431N     P=0.514N     P=0.528N     P=0.512N   |  P=0.004 **     (e)        P=0.526      P=0.055    |
|COCHRAN-ARMITAGE       |  P=0.431N                                          |  P=0.007 **                                        |
|FISHER EXACT           |               P=0.516N     P=0.533N     P=0.500N   |                 (e)        P=0.492      P=0.061    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/58 (2%)    4/56 (7%)    4/60 (7%)  |  5/60 (8%)    8/56 (14%)   4/58 (7%)    7/61 (11%) |
|ADJUSTED (b)           |   0.0%         2.4%         9.9%         9.6%      |  11.9%        17.9%         9.0%        20.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     1/5 (20%)    0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/39 (0%)    1/34 (3%)    2/38 (5%)  |  2/36 (6%)    3/39 (8%)    2/41 (5%)    4/29 (14%) |
|FIRST INCIDENCE (DAYS) |   ---          673          456 (I)      613       |   587          590          538          419       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.029 *    P=0.491      P=0.035 *    P=0.058    |  P=0.312      P=0.343      P=0.445N     P=0.276    |
|INCIDENTAL TUMOR       |  P=0.033 *    P=0.557      P=0.082      P=0.111    |  P=0.521N     P=0.251      P=0.618      P=0.448    |
|LOGISTIC REGRESSION    |  P=0.037 *    P=0.494      P=0.054      P=0.062    |  P=0.469      P=0.277      P=0.505      P=0.358    |
|COCHRAN-ARMITAGE       |  P=0.031 *                                         |  P=0.470                                           |
|FISHER EXACT           |               P=0.492      P=0.051      P=0.059    |               P=0.236      P=0.522N     P=0.393    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  16
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/58 (0%)    4/56 (7%)    4/60 (7%)  |  4/60 (7%)    8/56 (14%)   4/58 (7%)    7/61 (11%) |
|ADJUSTED (b)           |   0.0%         0.0%         9.9%         9.6%      |   9.3%        17.9%         9.0%        20.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     1/5 (20%)    0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/42 (0%)    0/39 (0%)    1/34 (3%)    2/38 (5%)  |  1/36 (3%)    3/39 (8%)    2/41 (5%)    4/29 (14%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          456 (I)      613       |   587          590          538          419       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.015 *      (e)        P=0.035 *    P=0.058    |  P=0.228      P=0.235      P=0.592N     P=0.187    |
|INCIDENTAL TUMOR       |  P=0.016 *      (e)        P=0.082      P=0.111    |  P=0.501      P=0.148      P=0.448      P=0.333    |
|LOGISTIC REGRESSION    |  P=0.018 *      (e)        P=0.054      P=0.062    |  P=0.373      P=0.175      P=0.319      P=0.249    |
|COCHRAN-ARMITAGE       |  P=0.015 *                                         |  P=0.369                                           |
|FISHER EXACT           |                 (e)        P=0.051      P=0.059    |               P=0.149      P=0.622      P=0.274    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 39/60 (65%)  36/58 (62%)  43/56 (77%)  40/60 (67%) | 19/60 (32%)  29/56 (52%)  29/58 (50%)  27/61 (44%) |
|ADJUSTED (b)           |  79.1%        73.1%        89.4%        82.9%      |  46.6%        65.8%        65.5%        67.7%      |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   6/7 (86%)    4/5 (80%)    3/10 (30%) |  2/9 (22%)    0/6 (0%)     2/8 (25%)    2/9 (22%)  |
|TERMINAL (d)           | 32/42 (76%)  26/39 (67%)  29/34 (85%)  30/38 (79%) | 15/36 (42%)  24/39 (62%)  26/41 (63%)  17/29 (59%) |
|FIRST INCIDENCE (DAYS) |   449          455 (I)      455 (I)      417       |   455 (I)      594          455 (I)      420       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.167      P=0.498      P=0.010 **   P=0.274    |  P=0.017 *    P=0.077      P=0.103      P=0.021 *  |
|INCIDENTAL TUMOR       |  P=0.310      P=0.534N     P=0.058      P=0.504    |  P=0.055      P=0.056      P=0.094      P=0.057    |
|LOGISTIC REGRESSION    |  P=0.329      P=0.432N     P=0.129      P=0.480    |  P=0.065      P=0.056      P=0.061      P=0.059    |
|COCHRAN-ARMITAGE       |  P=0.349                                           |  P=0.193                                           |
|FISHER EXACT           |               P=0.444N     P=0.117      P=0.500    |               P=0.022 *    P=0.033 *    P=0.107    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  17
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |   VEHICLE      200MG/KG     400MG/KG     800MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 17/60 (28%)  17/58 (29%)  16/56 (29%)  20/60 (33%) |  9/60 (15%)  11/56 (20%)  11/58 (19%)  16/61 (26%) |
|ADJUSTED (b)           |  35.9%        34.3%        36.2%        41.2%      |  20.6%        23.6%        22.8%        40.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/7 (0%)     1/5 (20%)    0/10 (0%)  |  0/9 (0%)     0/6 (0%)     0/8 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 12/42 (29%)   7/39 (18%)   7/34 (21%)  10/38 (26%) |  3/36 (8%)    4/39 (10%)   5/41 (12%)   7/29 (24%) |
|FIRST INCIDENCE (DAYS) |   456          423          456 (I)      417       |   587          590          444          419       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.236      P=0.504      P=0.443      P=0.270    |  P=0.027 *    P=0.483      P=0.501      P=0.047 *  |
|INCIDENTAL TUMOR       |  P=0.494      P=0.302N     P=0.229N     P=0.580N   |  P=0.235      P=0.343      P=0.277      P=0.178    |
|LOGISTIC REGRESSION    |  P=0.432      P=0.531N     P=0.314N     P=0.494    |  P=0.109      P=0.224      P=0.157      P=0.098    |
|COCHRAN-ARMITAGE       |  P=0.305                                           |  P=0.082                                           |
|FISHER EXACT           |               P=0.534      P=0.570      P=0.346    |               P=0.339      P=0.371      P=0.096    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 46/60 (77%)  46/58 (79%)  48/56 (86%)  47/60 (78%) | 26/60 (43%)  36/56 (64%)  38/58 (66%)  40/61 (66%) |
|ADJUSTED (b)           |  88.3%        83.6%        92.3%        90.3%      |  56.0%        73.5%        75.7%        83.0%      |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   6/7 (86%)    4/5 (80%)    3/10 (30%) |  2/9 (22%)    0/6 (0%)     2/8 (25%)    2/9 (22%)  |
|TERMINAL (d)           | 36/42 (86%)  30/39 (77%)  30/34 (88%)  33/38 (87%) | 16/36 (44%)  26/39 (67%)  29/41 (71%)  21/29 (72%) |
|FIRST INCIDENCE (DAYS) |   449          423          455 (I)      417       |   455 (I)      590          444          419       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.220      P=0.271      P=0.024 *    P=0.250    |  P<0.001 **   P=0.131      P=0.104      P=0.002 ** |
|INCIDENTAL TUMOR       |  P=0.529      P=0.560      P=0.331      P=0.573N   |  P=0.013 *    P=0.039 *    P=0.026 *    P=0.011 *  |
|LOGISTIC REGRESSION    |  P=0.500      P=0.464      P=0.178      P=0.489    |  P=0.006 **   P=0.028 *    P=0.026 *    P=0.004 ** |
|COCHRAN-ARMITAGE       |  P=0.441                                           |  P=0.020 *                                         |
|FISHER EXACT           |               P=0.451      P=0.157      P=0.500    |               P=0.019 *    P=0.013 *    P=0.011 *  |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05091 TEST: 02                                                 PAGE  18
                               STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- DIHYDROCOUMARIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   455
          Female interim sacrifices(days): 455
 (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).