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TDMS Study 05090-02 Pathology Tables


NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: American Biogenics                                         COUMARIN                                       DATE: 09/12/94       
EXPERIMENT: 05090 TEST: 02                                                                                     TIME: 06:36:35       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-45039          ROUTE: GAVAGE                                                                      NTP C#: 07103B       
PATHOLOGIST: R. DAHLGREN                                                                                       CAS: 91-64-5         
------------------------------------------------------------------------------------------------------------------------------------
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: American Biogenics                                         COUMARIN                                       DATE: 09/12/94      
EXPERIMENT: 05090 TEST: 02                                                                                     TIME: 06:36:35      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NO1-ES-45039          ROUTE: GAVAGE                                                                      NTP C#: 07103B      
PATHOLOGIST: R. DAHLGREN                                                                                       CAS: 91-64-5        
                                                    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
                                                    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                                         COUMARIN                                       DATE: 09/12/94       
EXPERIMENT: 05090 TEST: 02                                                                                     TIME: 06:36:35       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-45039          ROUTE: GAVAGE                                                                      NTP C#: 07103B       
PATHOLOGIST: R. DAHLGREN                                                                                       CAS: 91-64-5         
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                            IN THE ANALYSIS OF THE STUDY OF COUMARIN
              ====================================================================================================
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
                             Liver                         Hepatoblastoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Stomach, Forestomach          Squamous Cell Carcinoma or Papilloma Squamous
                             Testes                        Adenoma
                             Thyroid Gland: Follicular Cell
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Malignant Lymphoma And Histiocytic Sarcoma
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
              ====================================================================================================
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Uterus                        Sarcoma Stromal
                             All Organs                    Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
              ====================================================================================================
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   1
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    0/57 (0%)    0/55 (0%)    1/59 (2%)  |  2/57 (4%)    0/55 (0%)    0/55 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   2.3%         0.0%         0.0%         2.7%      |   6.3%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/43 (2%)    0/47 (0%)    0/41 (0%)    1/37 (3%)  |  2/32 (6%)    0/40 (0%)    0/42 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          729 (T)   |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.558      P=0.482N     P=0.510N     P=0.728    |  P=0.113N     P=0.191N     P=0.181N     P=0.268N   |
|INCIDENTAL TUMOR       |  P=0.558      P=0.482N     P=0.510N     P=0.728    |  P=0.113N     P=0.191N     P=0.181N     P=0.268N   |
|LOGISTIC REGRESSION    |  P=0.558      P=0.482N     P=0.510N     P=0.728    |  P=0.113N     P=0.191N     P=0.181N     P=0.268N   |
|COCHRAN-ARMITAGE       |  P=0.595                                           |  P=0.114N                                          |
|FISHER EXACT           |               P=0.509N     P=0.518N     P=0.752N   |               P=0.257N     P=0.257N     P=0.239N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    1/58 (2%)    1/57 (2%)    1/60 (2%)  |  1/60 (2%)    1/58 (2%)    1/58 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |   6.7%         2.1%         2.3%         1.9%      |   3.0%         2.5%         2.2%         3.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     1/9 (11%)  |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/43 (5%)    1/47 (2%)    0/42 (0%)    0/37 (0%)  |  1/33 (3%)    1/40 (3%)    0/42 (0%)    1/28 (4%)  |
|FIRST INCIDENCE (DAYS) |   680          729 (T)      723          456 (I)   |   729 (T)      729 (T)      679          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.290N     P=0.280N     P=0.320N     P=0.357N   |  P=0.591      P=0.718N     P=0.714N     P=0.725    |
|INCIDENTAL TUMOR       |  P=0.232N     P=0.401N     P=0.583N     P=0.328N   |  P=0.625      P=0.718N     P=0.745      P=0.725    |
|LOGISTIC REGRESSION    |  P=0.247N     P=0.299N     P=0.330N     P=0.297N   |  P=0.607      P=0.718N     P=0.740N     P=0.725    |
|COCHRAN-ARMITAGE       |  P=0.243N                                          |  P=0.630N                                          |
|FISHER EXACT           |               P=0.322N     P=0.329N     P=0.309N   |               P=0.744      P=0.744      P=0.752N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   2
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    2/58 (3%)    0/57 (0%)    0/60 (0%)  |  0/60 (0%)    0/58 (0%)    0/58 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   4.7%         4.3%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/43 (5%)    2/47 (4%)    0/42 (0%)    0/37 (0%)  |  0/33 (0%)    0/40 (0%)    0/42 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.102N     P=0.662N     P=0.244N     P=0.272N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.102N     P=0.662N     P=0.244N     P=0.272N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.102N     P=0.662N     P=0.244N     P=0.272N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.088N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.678      P=0.261N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/58 (2%)    0/57 (0%)    0/60 (0%)  |  0/60 (0%)    0/58 (0%)    0/58 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   4.7%         2.1%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/43 (5%)    1/47 (2%)    0/42 (0%)    0/37 (0%)  |  0/33 (0%)    0/40 (0%)    0/42 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.115N     P=0.469N     P=0.244N     P=0.272N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.115N     P=0.469N     P=0.244N     P=0.272N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.115N     P=0.469N     P=0.244N     P=0.272N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.102N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.513N     P=0.261N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   3
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    0/58 (0%)    3/57 (5%)    2/59 (3%)  |  1/57 (2%)    2/56 (4%)    1/55 (2%)    0/56 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         7.1%         5.4%      |   3.0%         5.0%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    0/47 (0%)    3/42 (7%)    2/37 (5%)  |  1/33 (3%)    2/40 (5%)    1/42 (2%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      729 (T)   |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.067        (e)        P=0.117      P=0.206    |  P=0.277N     P=0.567      P=0.707N     P=0.533N   |
|INCIDENTAL TUMOR       |  P=0.067        (e)        P=0.117      P=0.206    |  P=0.277N     P=0.567      P=0.707N     P=0.533N   |
|LOGISTIC REGRESSION    |  P=0.067        (e)        P=0.117      P=0.206    |  P=0.277N     P=0.567      P=0.707N     P=0.533N   |
|COCHRAN-ARMITAGE       |  P=0.099                                           |  P=0.252N                                          |
|FISHER EXACT           |                 (e)        P=0.115      P=0.248    |               P=0.493      P=0.743      P=0.504N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    0/58 (0%)    3/57 (5%)    2/59 (3%)  |  1/57 (2%)    3/56 (5%)    1/55 (2%)    0/56 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         7.1%         5.4%      |   3.0%         7.0%         2.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    0/47 (0%)    3/42 (7%)    2/37 (5%)  |  1/33 (3%)    2/40 (5%)    1/42 (2%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      729 (T)   |   729 (T)      635          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.067        (e)        P=0.117      P=0.206    |  P=0.225N     P=0.377      P=0.707N     P=0.533N   |
|INCIDENTAL TUMOR       |  P=0.067        (e)        P=0.117      P=0.206    |  P=0.234N     P=0.359      P=0.707N     P=0.533N   |
|LOGISTIC REGRESSION    |  P=0.067        (e)        P=0.117      P=0.206    |  P=0.210N     P=0.353      P=0.707N     P=0.533N   |
|COCHRAN-ARMITAGE       |  P=0.099                                           |  P=0.205N                                          |
|FISHER EXACT           |                 (e)        P=0.115      P=0.248    |               P=0.302      P=0.743      P=0.504N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   4
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatoblastoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/58 (0%)    5/57 (9%)    1/60 (2%)  |  0/58 (0%)    1/57 (2%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%        11.1%         2.7%      |   0.0%         2.5%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    0/47 (0%)    4/42 (10%)   1/37 (3%)  |  0/33 (0%)    1/40 (3%)    0/42 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---            1          729 (T)   |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.196        (e)        P=0.032 *    P=0.470    |  P=0.601N     P=0.538        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.299        (e)        P=0.060      P=0.470    |  P=0.601N     P=0.538        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.280        (e)        P=0.037 *    P=0.470    |  P=0.601N     P=0.538        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.246                                           |  P=0.564N                                          |
|FISHER EXACT           |                 (e)        P=0.025 *    P=0.500    |               P=0.496        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 26/60 (43%)  31/58 (53%)  30/57 (53%)  30/60 (50%) |  9/58 (16%)  26/57 (46%)  29/58 (50%)  12/59 (20%) |
|ADJUSTED (b)           |  56.5%        60.8%        68.0%        65.9%      |  24.8%        63.4%        62.9%        39.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    2/8 (25%)    1/7 (14%)    3/9 (33%)  |  1/8 (13%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 23/43 (53%)  27/47 (57%)  28/42 (67%)  22/37 (59%) |  7/33 (21%)  25/40 (63%)  25/42 (60%)  10/28 (36%) |
|FIRST INCIDENCE (DAYS) |   680          456 (I)      455 (I)      455 (I)   |   455 (I)      722          564          684       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.068      P=0.364      P=0.222      P=0.101    |  P=0.288      P=0.003 **   P=0.001 **   P=0.196    |
|INCIDENTAL TUMOR       |  P=0.165      P=0.232      P=0.158      P=0.152    |  P=0.389      P=0.002 **   P<0.001 **   P=0.253    |
|LOGISTIC REGRESSION    |  P=0.156      P=0.237      P=0.154      P=0.159    |  P=0.423      P=0.002 **   P<0.001 **   P=0.257    |
|COCHRAN-ARMITAGE       |  P=0.335                                           |  P=0.463N                                          |
|FISHER EXACT           |               P=0.180      P=0.206      P=0.292    |               P<0.001 **   P<0.001 **   P=0.331    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   5
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/60 (18%)  11/58 (19%)   5/57 (9%)    3/60 (5%)  |  0/58 (0%)    3/57 (5%)    3/58 (5%)    1/59 (2%)  |
|ADJUSTED (b)           |  23.6%        22.0%        11.6%         7.5%      |   0.0%         7.3%         6.7%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/43 (19%)   8/47 (17%)   4/42 (10%)   2/37 (5%)  |  0/33 (0%)    2/40 (5%)    1/42 (2%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   541          532          636          558       |   ---          715          672          655       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.018N*    P=0.520N     P=0.109N     P=0.045N*  |  P=0.465      P=0.162      P=0.162      P=0.484    |
|INCIDENTAL TUMOR       |  P=0.003N**   P=0.505      P=0.099N     P=0.011N*  |  P=0.570N     P=0.132      P=0.101      P=0.594    |
|LOGISTIC REGRESSION    |  P=0.002N**   P=0.493      P=0.104N     P=0.010N** |  P=0.582N     P=0.152      P=0.141      P=0.501    |
|COCHRAN-ARMITAGE       |  P=0.007N**                                        |  P=0.535                                           |
|FISHER EXACT           |               P=0.558      P=0.108N     P=0.022N*  |               P=0.119      P=0.122      P=0.504    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/60 (18%)  11/58 (19%)   9/57 (16%)   3/60 (5%)  |  0/58 (0%)    4/57 (7%)    3/58 (5%)    1/59 (2%)  |
|ADJUSTED (b)           |  23.6%        22.0%        20.0%         7.5%      |   0.0%         9.7%         6.7%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/43 (19%)   8/47 (17%)   7/42 (17%)   2/37 (5%)  |  0/33 (0%)    3/40 (8%)    1/42 (2%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   541          532            1          558       |   ---          715          672          655       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.034N*    P=0.520N     P=0.441N     P=0.045N*  |  P=0.533      P=0.094      P=0.162      P=0.484    |
|INCIDENTAL TUMOR       |  P=0.004N**   P=0.505      P=0.347N     P=0.011N*  |  P=0.502N     P=0.076      P=0.101      P=0.594    |
|LOGISTIC REGRESSION    |  P=0.017N*    P=0.493      P=0.460N     P=0.010N** |  P=0.571      P=0.086      P=0.141      P=0.501    |
|COCHRAN-ARMITAGE       |  P=0.014N*                                         |  P=0.586N                                          |
|FISHER EXACT           |               P=0.558      P=0.453N     P=0.022N*  |               P=0.057      P=0.122      P=0.504    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   6
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 35/60 (58%)  36/58 (62%)  32/57 (56%)  32/60 (53%) |  9/58 (16%)  27/57 (47%)  31/58 (53%)  13/59 (22%) |
|ADJUSTED (b)           |  71.4%        69.2%        71.0%        68.9%      |  24.8%        64.3%        65.9%        41.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    2/8 (25%)    1/7 (14%)    3/9 (33%)  |  1/8 (13%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 29/43 (67%)  31/47 (66%)  29/42 (69%)  23/37 (62%) |  7/33 (21%)  25/40 (63%)  26/42 (62%)  10/28 (36%) |
|FIRST INCIDENCE (DAYS) |   541          456 (I)      455 (I)      455 (I)   |   455 (I)      715          564          655       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.384      P=0.458N     P=0.435N     P=0.449    |  P=0.217      P=0.002 **   P<0.001 **   P=0.140    |
|INCIDENTAL TUMOR       |  P=0.345N     P=0.399      P=0.517N     P=0.447N   |  P=0.348      P<0.001 **   P<0.001 **   P=0.198    |
|LOGISTIC REGRESSION    |  P=0.362N     P=0.517      P=0.493N     P=0.525N   |  P=0.340      P=0.001 **   P<0.001 **   P=0.188    |
|COCHRAN-ARMITAGE       |  P=0.249N                                          |  P=0.536N                                          |
|FISHER EXACT           |               P=0.411      P=0.479N     P=0.357N   |               P<0.001 **   P<0.001 **   P=0.253    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 35/60 (58%)  36/58 (62%)  33/57 (58%)  32/60 (53%) |  9/58 (16%)  27/57 (47%)  31/58 (53%)  13/59 (22%) |
|ADJUSTED (b)           |  71.4%        69.2%        71.5%        68.9%      |  24.8%        64.3%        65.9%        41.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    2/8 (25%)    1/7 (14%)    3/9 (33%)  |  1/8 (13%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 29/43 (67%)  31/47 (66%)  29/42 (69%)  23/37 (62%) |  7/33 (21%)  25/40 (63%)  26/42 (62%)  10/28 (36%) |
|FIRST INCIDENCE (DAYS) |   541          456 (I)        1          455 (I)   |   455 (I)      715          564          655       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.377      P=0.458N     P=0.512N     P=0.449    |  P=0.217      P=0.002 **   P<0.001 **   P=0.140    |
|INCIDENTAL TUMOR       |  P=0.311N     P=0.399      P=0.517N     P=0.447N   |  P=0.348      P<0.001 **   P<0.001 **   P=0.198    |
|LOGISTIC REGRESSION    |  P=0.438N     P=0.517      P=0.541N     P=0.525N   |  P=0.340      P=0.001 **   P<0.001 **   P=0.188    |
|COCHRAN-ARMITAGE       |  P=0.255N                                          |  P=0.536N                                          |
|FISHER EXACT           |               P=0.411      P=0.555N     P=0.357N   |               P<0.001 **   P<0.001 **   P=0.253    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   7
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/60 (23%)  10/58 (17%)  14/57 (25%)  27/60 (45%) |  2/59 (3%)    5/57 (9%)    8/56 (14%)  22/60 (37%) |
|ADJUSTED (b)           |  29.7%        20.2%        33.3%        60.6%      |   5.8%        11.8%        18.0%        65.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    2/8 (25%)    0/7 (0%)     3/9 (33%)  |  0/8 (0%)     0/8 (0%)     1/7 (14%)    2/9 (22%)  |
|TERMINAL (d)           | 10/43 (23%)   8/47 (17%)  14/42 (33%)  20/37 (54%) |  1/33 (3%)    3/40 (8%)    6/42 (14%)  17/28 (61%) |
|FIRST INCIDENCE (DAYS) |   653          456 (I)      729 (T)      455 (I)   |   708          673          456 (I)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.210N     P=0.549      P=0.003 ** |  P<0.001 **   P=0.301      P=0.092      P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.413N     P=0.324      P=0.005 ** |  P<0.001 **   P=0.213      P=0.057      P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.251N     P=0.507      P=0.004 ** |  P<0.001 **   P=0.281      P=0.060      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.277N     P=0.524      P=0.010 *  |               P=0.205      P=0.039 *    P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    1/58 (2%)    2/57 (4%)    1/60 (2%)  |  0/59 (0%)    0/57 (0%)    0/56 (0%)    7/60 (12%) |
|ADJUSTED (b)           |   2.2%         2.1%         4.8%         2.7%      |   0.0%         0.0%         0.0%        22.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    1/47 (2%)    2/42 (5%)    1/37 (3%)  |  0/33 (0%)    0/40 (0%)    0/42 (0%)    5/28 (18%) |
|FIRST INCIDENCE (DAYS) |   716          729 (T)      729 (T)      729 (T)   |   ---          ---          ---          615       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.530      P=0.746N     P=0.489      P=0.722    |  P<0.001 **     (e)          (e)        P=0.006 ** |
|INCIDENTAL TUMOR       |  P=0.579      P=0.619      P=0.332      P=0.758N   |  P<0.001 **     (e)          (e)        P=0.007 ** |
|LOGISTIC REGRESSION    |  P=0.541      P=0.757N     P=0.478      P=0.736    |  P<0.001 **     (e)          (e)        P=0.007 ** |
|COCHRAN-ARMITAGE       |  P=0.592                                           |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.744      P=0.481      P=0.752N   |                 (e)          (e)        P=0.007 ** |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   8
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/60 (23%)  11/58 (19%)  15/57 (26%)  28/60 (47%) |  2/59 (3%)    5/57 (9%)    8/56 (14%)  29/60 (48%) |
|ADJUSTED (b)           |  29.7%        22.3%        35.7%        62.9%      |   5.8%        11.8%        18.0%        82.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    2/8 (25%)    0/7 (0%)     3/9 (33%)  |  0/8 (0%)     0/8 (0%)     1/7 (14%)    2/9 (22%)  |
|TERMINAL (d)           | 10/43 (23%)   9/47 (19%)  15/42 (36%)  21/37 (57%) |  1/33 (3%)    3/40 (8%)    6/42 (14%)  22/28 (79%) |
|FIRST INCIDENCE (DAYS) |   653          456 (I)      729 (T)      455 (I)   |   708          673          456 (I)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.279N     P=0.463      P=0.002 ** |  P<0.001 **   P=0.301      P=0.092      P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.504N     P=0.247      P=0.003 ** |  P<0.001 **   P=0.213      P=0.057      P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.331N     P=0.415      P=0.002 ** |  P<0.001 **   P=0.281      P=0.060      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.362N     P=0.436      P=0.006 ** |               P=0.205      P=0.039 *    P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/59 (3%)    3/57 (5%)    4/57 (7%)    2/60 (3%)  |
|ADJUSTED (b)           |                                                    |   6.1%         7.5%         9.5%         6.2%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  2/33 (6%)    3/40 (8%)    4/42 (10%)   1/28 (4%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   729 (T)      729 (T)      729 (T)      637       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.519      P=0.588      P=0.453      P=0.644    |
|INCIDENTAL TUMOR       |                                                    |  P=0.507      P=0.588      P=0.453      P=0.628    |
|LOGISTIC REGRESSION    |                                                    |  P=0.555      P=0.588      P=0.453      P=0.677    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.549N                                          |
|FISHER EXACT           |                                                    |               P=0.484      P=0.323      P=0.684N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE   9
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/52 (0%)    0/54 (0%)    0/47 (0%)    0/48 (0%)  |  4/53 (8%)    3/53 (6%)    4/52 (8%)    0/57 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  10.7%         7.7%        10.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/37 (0%)    0/44 (0%)    0/35 (0%)    0/29 (0%)  |  2/30 (7%)    3/39 (8%)    4/37 (11%)   0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   367          729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.082N     P=0.383N     P=0.543N     P=0.080N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.072N     P=0.428N     P=0.567      P=0.052N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.058N     P=0.455N     P=0.611N     P=0.054N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.056N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.500N     P=0.631      P=0.051N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/58 (2%)    2/57 (4%)    0/60 (0%)  |  0/60 (0%)    1/58 (2%)    1/58 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         2.1%         3.9%         0.0%      |   0.0%         2.5%         2.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    1/47 (2%)    0/42 (0%)    0/37 (0%)  |  0/33 (0%)    1/40 (3%)    0/42 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)        1          ---       |   ---          729 (T)      694          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.639N     P=0.518      P=0.230        (e)      |  P=0.636N     P=0.538      P=0.535        (e)      |
|INCIDENTAL TUMOR       |  P=0.289N     P=0.518        (e)          (e)      |  P=0.573N     P=0.538      P=0.419        (e)      |
|LOGISTIC REGRESSION    |  P=0.498N     P=0.518      P=0.477        (e)      |  P=0.620N     P=0.538      P=0.517        (e)      |
|COCHRAN-ARMITAGE       |  P=0.613N                                          |  P=0.593N                                          |
|FISHER EXACT           |               P=0.492      P=0.235        (e)      |               P=0.492      P=0.492        (e)      |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE  10
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    9/58 (16%)   4/57 (7%)    0/60 (0%)  |  1/60 (2%)    6/58 (10%)   3/58 (5%)    2/60 (3%)  |
|ADJUSTED (b)           |   4.7%        19.1%         8.5%         0.0%      |   2.4%        15.0%         7.0%         7.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/43 (5%)    9/47 (19%)   2/42 (5%)    0/37 (0%)  |  0/33 (0%)    6/40 (15%)   2/42 (5%)    2/28 (7%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)        1          ---       |   589          729 (T)      694          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.100N     P=0.039 *    P=0.326      P=0.272N   |  P=0.575      P=0.095      P=0.376      P=0.456    |
|INCIDENTAL TUMOR       |  P=0.042N*    P=0.039 *    P=0.686      P=0.272N   |  P=0.578N     P=0.083      P=0.236      P=0.436    |
|LOGISTIC REGRESSION    |  P=0.073N     P=0.039 *    P=0.372      P=0.272N   |  P=0.558N     P=0.083      P=0.327      P=0.486    |
|COCHRAN-ARMITAGE       |  P=0.069N                                          |  P=0.496N                                          |
|FISHER EXACT           |               P=0.023 *    P=0.315      P=0.248N   |               P=0.052      P=0.297      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    8/58 (14%)   2/57 (4%)    0/60 (0%)  |  1/60 (2%)    5/58 (9%)    2/58 (3%)    2/60 (3%)  |
|ADJUSTED (b)           |   4.7%        17.0%         4.8%         0.0%      |   2.4%        12.5%         4.8%         7.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/43 (5%)    8/47 (17%)   2/42 (5%)    0/37 (0%)  |  0/33 (0%)    5/40 (13%)   2/42 (5%)    2/28 (7%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      ---       |   589          729 (T)      729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.078N     P=0.064      P=0.686      P=0.272N   |  P=0.552      P=0.152      P=0.566      P=0.456    |
|INCIDENTAL TUMOR       |  P=0.078N     P=0.064      P=0.686      P=0.272N   |  P=0.542      P=0.134      P=0.455      P=0.436    |
|LOGISTIC REGRESSION    |  P=0.078N     P=0.064      P=0.686      P=0.272N   |  P=0.583      P=0.135      P=0.521      P=0.486    |
|COCHRAN-ARMITAGE       |  P=0.055N                                          |  P=0.540N                                          |
|FISHER EXACT           |               P=0.042 *    P=0.671      P=0.248N   |               P=0.096      P=0.487      P=0.500    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE  11
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/59 (5%)    0/58 (0%)    0/57 (0%)    0/59 (0%)  |                                                    |
|ADJUSTED (b)           |   7.0%         0.0%         0.0%         0.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |                                                    |
|TERMINAL (d)           |  3/43 (7%)    0/47 (0%)    0/42 (0%)    0/37 (0%)  |                                                    |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          ---       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.054N     P=0.106N     P=0.125N     P=0.149N   |                                                    |
|INCIDENTAL TUMOR       |  P=0.054N     P=0.106N     P=0.125N     P=0.149N   |                                                    |
|LOGISTIC REGRESSION    |  P=0.054N     P=0.106N     P=0.125N     P=0.149N   |                                                    |
|COCHRAN-ARMITAGE       |  P=0.048N*                                         |                                                    |
|FISHER EXACT           |               P=0.125N     P=0.128N     P=0.122N   |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    2/58 (3%)    0/57 (0%)    0/60 (0%)  |  0/55 (0%)    0/57 (0%)    0/57 (0%)    0/56 (0%)  |
|ADJUSTED (b)           |   0.0%         4.3%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    2/47 (4%)    0/42 (0%)    0/37 (0%)  |  0/32 (0%)    0/40 (0%)    0/42 (0%)    0/28 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.441N     P=0.258        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.441N     P=0.258        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.441N     P=0.258        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.402N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.244        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE  12
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    0/58 (0%)    0/57 (0%)    2/60 (3%)  |  0/55 (0%)    0/57 (0%)    1/57 (2%)    1/56 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         5.4%      |   0.0%         0.0%         2.4%         3.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    0/47 (0%)    0/42 (0%)    2/37 (5%)  |  0/32 (0%)    0/40 (0%)    1/42 (2%)    1/28 (4%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          729 (T)   |   ---          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.033 *      (e)          (e)        P=0.206    |  P=0.191        (e)        P=0.554      P=0.473    |
|INCIDENTAL TUMOR       |  P=0.033 *      (e)          (e)        P=0.206    |  P=0.191        (e)        P=0.554      P=0.473    |
|LOGISTIC REGRESSION    |  P=0.033 *      (e)          (e)        P=0.206    |  P=0.191        (e)        P=0.554      P=0.473    |
|COCHRAN-ARMITAGE       |  P=0.049 *                                         |  P=0.236                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.252    |                 (e)        P=0.509      P=0.505    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    0/58 (0%)    0/57 (0%)    2/60 (3%)  |  1/55 (2%)    0/57 (0%)    1/57 (2%)    1/56 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         5.4%      |   3.1%         0.0%         2.4%         3.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    0/47 (0%)    0/42 (0%)    2/37 (5%)  |  1/32 (3%)    0/40 (0%)    1/42 (2%)    1/28 (4%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          729 (T)   |   729 (T)      ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.033 *      (e)          (e)        P=0.206    |  P=0.498      P=0.455N     P=0.700N     P=0.732    |
|INCIDENTAL TUMOR       |  P=0.033 *      (e)          (e)        P=0.206    |  P=0.498      P=0.455N     P=0.700N     P=0.732    |
|LOGISTIC REGRESSION    |  P=0.033 *      (e)          (e)        P=0.206    |  P=0.498      P=0.455N     P=0.700N     P=0.734    |
|COCHRAN-ARMITAGE       |  P=0.049 *                                         |  P=0.542                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.252    |               P=0.491N     P=0.743N     P=0.748N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE  13
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/60 (0%)    0/58 (0%)    0/58 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |                                                    |   0.0%         0.0%         0.0%         6.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  0/33 (0%)    0/40 (0%)    0/42 (0%)    1/28 (4%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          ---          ---          615       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.032 *      (e)          (e)        P=0.219    |
|INCIDENTAL TUMOR       |                                                    |  P=0.036 *      (e)          (e)        P=0.198    |
|LOGISTIC REGRESSION    |                                                    |  P=0.042 *      (e)          (e)        P=0.231    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.048 *                                         |
|FISHER EXACT           |                                                    |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/60 (0%)    1/58 (2%)    0/58 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |                                                    |   0.0%         2.5%         0.0%         6.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  0/33 (0%)    1/40 (3%)    0/42 (0%)    1/28 (4%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          729 (T)      ---          615       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.106      P=0.538        (e)        P=0.219    |
|INCIDENTAL TUMOR       |                                                    |  P=0.107      P=0.538        (e)        P=0.198    |
|LOGISTIC REGRESSION    |                                                    |  P=0.124      P=0.538        (e)        P=0.231    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.143                                           |
|FISHER EXACT           |                                                    |               P=0.492        (e)        P=0.248    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE  14
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    3/58 (5%)    4/57 (7%)    4/60 (7%)  |  6/60 (10%)  12/58 (21%)   8/58 (14%)   5/60 (8%)  |
|ADJUSTED (b)           |   0.0%         6.4%         9.2%        10.5%      |  15.6%        26.8%        18.5%        17.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    3/47 (6%)    3/42 (7%)    3/37 (8%)  |  3/33 (9%)    8/40 (20%)   7/42 (17%)   5/28 (18%) |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      567          712       |   550          495          672          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.047 *    P=0.138      P=0.062      P=0.047 *  |  P=0.367N     P=0.200      P=0.550      P=0.598N   |
|INCIDENTAL TUMOR       |  P=0.082      P=0.138      P=0.117      P=0.056    |  P=0.307N     P=0.103      P=0.379      P=0.593N   |
|LOGISTIC REGRESSION    |  P=0.059      P=0.138      P=0.055      P=0.047 *  |  P=0.299N     P=0.121      P=0.459      P=0.539N   |
|COCHRAN-ARMITAGE       |  P=0.082                                           |  P=0.243N                                          |
|FISHER EXACT           |               P=0.116      P=0.053      P=0.059    |               P=0.087      P=0.363      P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    3/58 (5%)    4/57 (7%)    3/60 (5%)  |  5/60 (8%)   11/58 (19%)   8/58 (14%)   5/60 (8%)  |
|ADJUSTED (b)           |   0.0%         6.4%         9.2%         7.9%      |  13.3%        25.3%        18.5%        17.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/43 (0%)    3/47 (6%)    3/42 (7%)    2/37 (5%)  |  3/33 (9%)    8/40 (20%)   7/42 (17%)   5/28 (18%) |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      567          712       |   550          635          672          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.111      P=0.138      P=0.062      P=0.097    |  P=0.496N     P=0.176      P=0.427      P=0.536    |
|INCIDENTAL TUMOR       |  P=0.175      P=0.138      P=0.117      P=0.116    |  P=0.465N     P=0.111      P=0.288      P=0.516    |
|LOGISTIC REGRESSION    |  P=0.132      P=0.138      P=0.055      P=0.099    |  P=0.432N     P=0.133      P=0.339      P=0.594    |
|COCHRAN-ARMITAGE       |  P=0.167                                           |  P=0.351N                                          |
|FISHER EXACT           |               P=0.116      P=0.053      P=0.122    |               P=0.078      P=0.257      P=0.628N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE  15
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 38/60 (63%)  38/58 (66%)  37/57 (65%)  44/60 (73%) | 21/60 (35%)  33/58 (57%)  34/58 (59%)  28/60 (47%) |
|ADJUSTED (b)           |  79.2%        73.0%        82.1%        86.0%      |  51.6%        76.7%        70.7%        79.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    3/8 (38%)    1/7 (14%)    6/9 (67%)  |  1/8 (13%)    0/8 (0%)     1/7 (14%)    2/9 (22%)  |
|TERMINAL (d)           | 33/43 (77%)  33/47 (70%)  34/42 (81%)  30/37 (81%) | 14/33 (42%)  30/40 (75%)  28/42 (67%)  21/28 (75%) |
|FIRST INCIDENCE (DAYS) |   653          456 (I)      455 (I)      455 (I)   |   367          673          456 (I)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006 **   P=0.371N     P=0.569      P=0.026 *  |  P=0.031 *    P=0.125      P=0.130      P=0.044 *  |
|INCIDENTAL TUMOR       |  P=0.027 *    P=0.553      P=0.308      P=0.048 *  |  P=0.056      P=0.054      P=0.013 *    P=0.057    |
|LOGISTIC REGRESSION    |  P=0.027 *    P=0.558N     P=0.436      P=0.048 *  |  P=0.067      P=0.067      P=0.027 *    P=0.067    |
|COCHRAN-ARMITAGE       |  P=0.138                                           |  P=0.229                                           |
|FISHER EXACT           |               P=0.478      P=0.506      P=0.163    |               P=0.014 *    P=0.008 **   P=0.133    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 15/60 (25%)  14/58 (24%)  16/57 (28%)   8/60 (13%) |  8/60 (13%)  19/58 (33%)  13/58 (22%)  14/60 (23%) |
|ADJUSTED (b)           |  31.1%        28.0%        34.4%        20.2%      |  19.5%        40.2%        28.9%        42.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/8 (0%)     0/7 (0%)     0/9 (0%)   |  0/8 (0%)     0/8 (0%)     0/7 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 10/43 (23%)  11/47 (23%)  12/42 (29%)   6/37 (16%) |  3/33 (9%)   12/40 (30%)  10/42 (24%)  10/28 (36%) |
|FIRST INCIDENCE (DAYS) |   541          532            1          558       |   474          495          672          615       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.175N     P=0.416N     P=0.456      P=0.164N   |  P=0.138      P=0.059      P=0.330      P=0.073    |
|INCIDENTAL TUMOR       |  P=0.023N*    P=0.494      P=0.585N     P=0.054N   |  P=0.225      P=0.008 **   P=0.084      P=0.081    |
|LOGISTIC REGRESSION    |  P=0.096N     P=0.503N     P=0.416      P=0.053N   |  P=0.211      P=0.015 *    P=0.130      P=0.096    |
|COCHRAN-ARMITAGE       |  P=0.073N                                          |  P=0.292                                           |
|FISHER EXACT           |               P=0.542N     P=0.434      P=0.082N   |               P=0.010 *    P=0.147      P=0.119    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 02                                                 PAGE  16
                                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |   VEHICLE      50 MG/KG     100MG/KG     200MG/KG  |
|                       |   CONTROL                                          |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 42/60 (70%)  43/58 (74%)  43/57 (75%)  45/60 (75%) | 26/60 (43%)  41/58 (71%)  37/58 (64%)  36/60 (60%) |
|ADJUSTED (b)           |  85.7%        81.1%        89.5%        88.0%      |  57.2%        87.2%        75.5%        92.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    3/8 (38%)    1/7 (14%)    6/9 (67%)  |  1/8 (13%)    0/8 (0%)     1/7 (14%)    2/9 (22%)  |
|TERMINAL (d)           | 36/43 (84%)  37/47 (79%)  37/42 (88%)  31/37 (84%) | 14/33 (42%)  34/40 (85%)  30/42 (71%)  25/28 (89%) |
|FIRST INCIDENCE (DAYS) |   541          456 (I)        1          455 (I)   |   367          495          456 (I)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.023 *    P=0.418N     P=0.386      P=0.066    |  P=0.013 *    P=0.089      P=0.271      P=0.017 *  |
|INCIDENTAL TUMOR       |  P=0.170      P=0.428      P=0.384      P=0.147    |  P=0.018 *    P=0.005 **   P=0.008 **   P=0.011 *  |
|LOGISTIC REGRESSION    |  P=0.102      P=0.518      P=0.277      P=0.136    |  P=0.024 *    P=0.018 *    P=0.059      P=0.017 *  |
|COCHRAN-ARMITAGE       |  P=0.321                                           |  P=0.135                                           |
|FISHER EXACT           |               P=0.384      P=0.326      P=0.342    |               P=0.002 **   P=0.020 *    P=0.050 *  |
|=================================================================================================================================|
 (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).