https://ntp.niehs.nih.gov/go/1135

TDMS Study 05090-01 Pathology Tables


NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: American Biogenics                                         COUMARIN                                       DATE: 09/12/94       
EXPERIMENT: 05090 TEST: 01                                                                                     TIME: 03:29:00       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01ES45039            ROUTE: GAVAGE                                                                      NTP C#: 07103B       
PATHOLOGIST: R. DAHLGREN                                                                                       CAS: 000091645       
------------------------------------------------------------------------------------------------------------------------------------
               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: 01                                                                                     TIME: 03:29:00      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01ES45039            ROUTE: GAVAGE                                                                      NTP C#: 07103B      
PATHOLOGIST: R. DAHLGREN                                                                                       CAS: 000091645      
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                    ----------------
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    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: 01                                                                                     TIME: 03:29:00       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES45039            ROUTE: GAVAGE                                                                      NTP C#: 07103B       
PATHOLOGIST: R. DAHLGREN                                                                                       CAS: 000091645       
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                            IN THE ANALYSIS OF THE STUDY OF COUMARIN
              ====================================================================================================
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
                             Adrenal Medulla               Pheochromocytoma Benign
                             Kidney: Renal Tubule          Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Testes                        Adenoma
                             Thyroid Gland: Follicular Cell
                                                           Carcinoma or Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
              ====================================================================================================
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma or Adenoma
                             Kidney: Renal Tubule          Adenoma
                             Mammary Gland                 Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)
                                                           Papilloma Squamous or Papilloma
                                                           Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma
                             Pharynx                       Squamous Cell Papilloma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Thyroid Gland: C-Cell         Carcinoma or Adenoma
              ====================================================================================================
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   1
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  9/89 (10%)   5/60 (8%)    5/59 (8%)    5/130 (4%) |  3/60 (5%)    2/60 (3%)    2/58 (3%)    1/59 (2%)  |
|ADJUSTED (b)           |  27.2%        29.9%        61.1%        40.1%      |   9.1%         5.3%         5.7%         3.3%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  5/28 (18%)   2/9 (22%)    1/2 (50%)    4/11 (36%) |  2/29 (7%)    2/38 (5%)    2/35 (6%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   573          503          506          680       |   607          729 (T)      729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.412      P=0.468      P=0.055      P=0.449    |  P=0.235N     P=0.401N     P=0.434N     P=0.295N   |
|INCIDENTAL TUMOR       |  P=0.314N     P=0.286N     P=0.566N     P=0.443N   |  P=0.216N     P=0.525N     P=0.432N     P=0.281N   |
|LOGISTIC REGRESSION    |  P=0.315N     P=0.404N     P=0.491      P=0.536N   |  P=0.238N     P=0.469N     P=0.506N     P=0.301N   |
|COCHRAN-ARMITAGE       |  P=0.042N*                                         |  P=0.240N                                          |
|FISHER EXACT           |               P=0.475N     P=0.488N     P=0.058N   |               P=0.500N     P=0.516N     P=0.316N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/85 (2%)    1/59 (2%)    1/59 (2%)    1/126 (1%) |  0/58 (0%)    6/57 (11%)   0/58 (0%)    2/59 (3%)  |
|ADJUSTED (b)           |   7.1%         5.0%         3.6%         9.1%      |   0.0%        15.9%         0.0%         6.3%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  2/28 (7%)    0/9 (0%)     0/2 (0%)     1/11 (9%)  |  0/29 (0%)    5/36 (14%)   0/34 (0%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      666          580          729 (T)   |   ---          659          ---          693       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.564      P=0.679      P=0.526      P=0.676    |  P=0.580      P=0.031 *      (e)        P=0.234    |
|INCIDENTAL TUMOR       |  P=0.526N     P=0.625N     P=0.799      P=0.676    |  P=0.588      P=0.020 *      (e)        P=0.233    |
|LOGISTIC REGRESSION    |  P=0.509N     P=0.675N     P=0.727      P=0.676    |  P=0.593      P=0.019 *      (e)        P=0.238    |
|COCHRAN-ARMITAGE       |  P=0.261N                                          |  P=0.586N                                          |
|FISHER EXACT           |               P=0.635N     P=0.635N     P=0.355N   |               P=0.013 *      (e)        P=0.252    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   2
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/85 (1%)    1/59 (2%)    0/59 (0%)    2/126 (2%) |  0/58 (0%)    1/57 (2%)    1/58 (2%)    2/59 (3%)  |
|ADJUSTED (b)           |   3.6%         2.9%         0.0%        10.5%      |   0.0%         2.8%         2.9%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     1/11 (9%)  |  0/29 (0%)    1/36 (3%)    1/34 (3%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      615          ---          525       |   ---          729 (T)      729 (T)      642       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.262      P=0.632      P=0.959N     P=0.334    |  P=0.144      P=0.543      P=0.532      P=0.246    |
|INCIDENTAL TUMOR       |  P=0.419      P=0.769      P=0.959N     P=0.428    |  P=0.174      P=0.543      P=0.532      P=0.264    |
|LOGISTIC REGRESSION    |  P=0.396      P=0.710      P=0.959N     P=0.507    |  P=0.154      P=0.543      P=0.532      P=0.243    |
|COCHRAN-ARMITAGE       |  P=0.534                                           |  P=0.158                                           |
|FISHER EXACT           |               P=0.653      P=0.590N     P=0.645    |               P=0.496      P=0.500      P=0.252    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/85 (4%)    2/59 (3%)    1/59 (2%)    3/126 (2%) |  0/58 (0%)    7/57 (12%)   1/58 (2%)    4/59 (7%)  |
|ADJUSTED (b)           |  10.7%         7.8%         3.6%        19.5%      |   0.0%        18.6%         2.9%        11.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  3/28 (11%)   0/9 (0%)     0/2 (0%)     2/11 (18%) |  0/29 (0%)    6/36 (17%)   1/34 (3%)    2/30 (7%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      615          580          525       |   ---          659          729 (T)      642       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.299      P=0.531      P=0.565      P=0.322    |  P=0.252      P=0.018 *    P=0.532      P=0.066    |
|INCIDENTAL TUMOR       |  P=0.515      P=0.614N     P=0.805N     P=0.389    |  P=0.290      P=0.011 *    P=0.532      P=0.071    |
|LOGISTIC REGRESSION    |  P=0.522      P=0.653N     P=0.720N     P=0.542    |  P=0.271      P=0.010 *    P=0.532      P=0.065    |
|COCHRAN-ARMITAGE       |  P=0.370N                                          |  P=0.285                                           |
|FISHER EXACT           |               P=0.668N     P=0.457N     P=0.462N   |               P=0.006 **   P=0.500      P=0.061    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   3
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/86 (5%)    1/60 (2%)    2/59 (3%)    1/128 (1%) |  1/59 (2%)    0/59 (0%)    1/58 (2%)    2/57 (4%)  |
|ADJUSTED (b)           |  13.3%        11.1%        27.9%         2.2%      |   3.3%         0.0%         2.9%         6.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  3/28 (11%)   1/9 (11%)    0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    1/35 (3%)    2/30 (7%)  |
|FIRST INCIDENCE (DAYS) |   660          729 (T)      588          588       |   719          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.426N     P=0.554N     P=0.207      P=0.415N   |  P=0.227      P=0.453N     P=0.719N     P=0.508    |
|INCIDENTAL TUMOR       |  P=0.222N     P=0.405N     P=0.705      P=0.199N   |  P=0.242      P=0.621N     P=0.657      P=0.497    |
|LOGISTIC REGRESSION    |  P=0.238N     P=0.406N     P=0.586      P=0.228N   |  P=0.222      P=0.479N     P=0.751N     P=0.491    |
|COCHRAN-ARMITAGE       |  P=0.078N                                          |  P=0.238                                           |
|FISHER EXACT           |               P=0.315N     P=0.530N     P=0.086N   |               P=0.500N     P=0.748      P=0.487    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/88 (1%)    2/60 (3%)    3/60 (5%)    4/130 (3%) |  0/59 (0%)    0/60 (0%)    0/60 (0%)    2/59 (3%)  |
|ADJUSTED (b)           |   3.6%         6.4%        13.8%        20.4%      |   0.0%         0.0%         0.0%         6.4%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    1/9 (11%)    0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     2/11 (18%) |  0/29 (0%)    0/38 (0%)    0/36 (0%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      583          455 (I)      496       |   ---          ---          ---          699       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.082      P=0.337      P=0.041 *    P=0.086    |  P=0.037 *      (e)          (e)        P=0.234    |
|INCIDENTAL TUMOR       |  P=0.252      P=0.559      P=0.238      P=0.135    |  P=0.055        (e)          (e)        P=0.233    |
|LOGISTIC REGRESSION    |  P=0.222      P=0.407      P=0.175      P=0.207    |  P=0.043 *      (e)          (e)        P=0.237    |
|COCHRAN-ARMITAGE       |  P=0.329                                           |  P=0.046 *                                         |
|FISHER EXACT           |               P=0.359      P=0.182      P=0.328    |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   4
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Oncocytoma Benign                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/88 (0%)    0/60 (0%)    0/60 (0%)    2/130 (2%) |  0/59 (0%)    0/60 (0%)    0/60 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         4.1%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          565       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.068        (e)          (e)        P=0.275    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.170        (e)          (e)        P=0.619    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.093        (e)          (e)        P=0.301    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.111                                           |    (e)                                             |
|FISHER EXACT           |                 (e)          (e)        P=0.355    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/89 (0%)    0/60 (0%)    0/60 (0%)    2/130 (2%) |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         3.8%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     1/20 (5%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          453 (I)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.072        (e)          (e)        P=0.251    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.125        (e)          (e)        P=0.418    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.106        (e)          (e)        P=0.318    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.110                                           |    (e)                                             |
|FISHER EXACT           |                 (e)          (e)        P=0.351    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   5
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/89 (2%)    0/60 (0%)    0/60 (0%)    0/130 (0%) |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   6.8%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   720          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.285N     P=0.517N     P=0.857N     P=0.458N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.194N     P=0.228N     P=0.480N     P=0.289N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.265N     P=0.460N     P=0.800N     P=0.425N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.091N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.355N     P=0.355N     P=0.164N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/89 (2%)    0/60 (0%)    0/60 (0%)    2/130 (2%) |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   6.8%         0.0%         0.0%         3.8%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     1/20 (5%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   720          ---          ---          453 (I)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.369      P=0.517N     P=0.857N     P=0.540    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.541      P=0.228N     P=0.480N     P=0.612N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.553      P=0.460N     P=0.800N     P=0.651N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.589N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.355N     P=0.355N     P=0.537N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   6
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/89 (2%)    0/60 (0%)    0/60 (0%)    2/130 (2%) |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   6.8%         0.0%         0.0%         3.8%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     1/20 (5%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   720          ---          ---          453 (I)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.369      P=0.517N     P=0.857N     P=0.540    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.541      P=0.228N     P=0.480N     P=0.612N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.553      P=0.460N     P=0.800N     P=0.651N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.589N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.355N     P=0.355N     P=0.537N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/89 (1%)    2/59 (3%)    1/59 (2%)    1/130 (1%) |  0/60 (0%)    1/59 (2%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.6%        10.0%         2.0%         1.3%      |   0.0%         2.6%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    1/9 (11%)    0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    1/38 (3%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      652          455 (I)      496       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.590      P=0.262      P=0.436      P=0.734    |  P=0.576N     P=0.554        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.490N     P=0.596      P=0.436      P=0.751N   |  P=0.576N     P=0.554        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.419N     P=0.374      P=0.671      P=0.723N   |  P=0.576N     P=0.554        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.358N                                          |  P=0.566N                                          |
|FISHER EXACT           |               P=0.349      P=0.640      P=0.649N   |               P=0.496        (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   7
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/89 (0%)    0/60 (0%)    0/60 (0%)    1/130 (1%) |  1/60 (2%)    2/60 (3%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         4.0%      |   3.4%         5.3%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  1/29 (3%)    2/38 (5%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          638       |   729 (T)      729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.173        (e)          (e)        P=0.433    |  P=0.183N     P=0.594      P=0.457N     P=0.493N   |
|INCIDENTAL TUMOR       |  P=0.374        (e)          (e)        P=0.810    |  P=0.183N     P=0.594      P=0.457N     P=0.493N   |
|LOGISTIC REGRESSION    |  P=0.227        (e)          (e)        P=0.520    |  P=0.183N     P=0.594      P=0.457N     P=0.493N   |
|COCHRAN-ARMITAGE       |  P=0.286                                           |  P=0.188N                                          |
|FISHER EXACT           |                 (e)          (e)        P=0.594    |               P=0.500      P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/89 (0%)    0/60 (0%)    0/60 (0%)    1/130 (1%) |  2/60 (3%)    2/60 (3%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         4.0%      |   6.9%         5.3%         0.0%         3.3%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  2/29 (7%)    2/38 (5%)    0/36 (0%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          638       |   729 (T)      729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.173        (e)          (e)        P=0.433    |  P=0.298N     P=0.594N     P=0.192N     P=0.488N   |
|INCIDENTAL TUMOR       |  P=0.374        (e)          (e)        P=0.810    |  P=0.298N     P=0.594N     P=0.192N     P=0.488N   |
|LOGISTIC REGRESSION    |  P=0.227        (e)          (e)        P=0.520    |  P=0.298N     P=0.594N     P=0.192N     P=0.488N   |
|COCHRAN-ARMITAGE       |  P=0.286                                           |  P=0.296N                                          |
|FISHER EXACT           |                 (e)          (e)        P=0.594    |               P=0.691N     P=0.248N     P=0.500N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   8
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/89 (4%)    1/60 (2%)    2/60 (3%)    2/130 (2%) | 17/60 (28%)  24/60 (40%)  22/60 (37%)  11/60 (18%) |
|ADJUSTED (b)           |  10.5%         3.1%        10.8%        18.2%      |  48.2%        57.0%        59.5%        29.8%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  1/17 (6%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     2/11 (18%) | 12/29 (41%)  20/38 (53%)  21/36 (58%)   6/30 (20%) |
|FIRST INCIDENCE (DAYS) |   455 (I)      625          533          729 (T)   |   491          659          709          551       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.553N     P=0.335N     P=0.535      P=0.616N   |  P=0.065N     P=0.393      P=0.470      P=0.131N   |
|INCIDENTAL TUMOR       |  P=0.233N     P=0.134N     P=0.261N     P=0.391N   |  P=0.044N*    P=0.155      P=0.252      P=0.101N   |
|LOGISTIC REGRESSION    |  P=0.290N     P=0.270N     P=0.535N     P=0.321N   |  P=0.050N     P=0.165      P=0.236      P=0.121N   |
|COCHRAN-ARMITAGE       |  P=0.175N                                          |  P=0.059N                                          |
|FISHER EXACT           |               P=0.329N     P=0.539N     P=0.185N   |               P=0.124      P=0.218      P=0.140N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/89 (4%)    1/60 (2%)    2/60 (3%)    3/130 (2%) | 18/60 (30%)  25/60 (42%)  22/60 (37%)  11/60 (18%) |
|ADJUSTED (b)           |  10.5%         3.1%        10.8%        21.5%      |  51.3%        59.4%        59.5%        29.8%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  1/17 (6%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     2/11 (18%) | 13/29 (45%)  21/38 (55%)  21/36 (58%)   6/30 (20%) |
|FIRST INCIDENCE (DAYS) |   455 (I)      625          533          638       |   491          659          709          551       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.411      P=0.335N     P=0.535      P=0.526    |  P=0.039N*    P=0.414      P=0.564      P=0.093N   |
|INCIDENTAL TUMOR       |  P=0.350N     P=0.134N     P=0.261N     P=0.454N   |  P=0.025N*    P=0.169      P=0.337      P=0.068N   |
|LOGISTIC REGRESSION    |  P=0.468N     P=0.270N     P=0.535N     P=0.481N   |  P=0.029N*    P=0.170      P=0.310      P=0.084N   |
|COCHRAN-ARMITAGE       |  P=0.304N                                          |  P=0.037N*                                         |
|FISHER EXACT           |               P=0.329N     P=0.539N     P=0.300N   |               P=0.127      P=0.281      P=0.100N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE   9
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/89 (4%)    1/60 (2%)    2/60 (3%)    3/130 (2%) | 19/60 (32%)  25/60 (42%)  22/60 (37%)  12/60 (20%) |
|ADJUSTED (b)           |  10.5%         3.1%        10.8%        21.5%      |  54.3%        59.4%        59.5%        32.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  1/17 (6%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     2/11 (18%) | 14/29 (48%)  21/38 (55%)  21/36 (58%)   7/30 (23%) |
|FIRST INCIDENCE (DAYS) |   455 (I)      625          533          638       |   491          659          709          551       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.411      P=0.335N     P=0.535      P=0.526    |  P=0.044N*    P=0.502      P=0.512N     P=0.095N   |
|INCIDENTAL TUMOR       |  P=0.350N     P=0.134N     P=0.261N     P=0.454N   |  P=0.029N*    P=0.236      P=0.432      P=0.070N   |
|LOGISTIC REGRESSION    |  P=0.468N     P=0.270N     P=0.535N     P=0.481N   |  P=0.034N*    P=0.230      P=0.391      P=0.087N   |
|COCHRAN-ARMITAGE       |  P=0.304N                                          |  P=0.042N*                                         |
|FISHER EXACT           |               P=0.329N     P=0.539N     P=0.300N   |               P=0.172      P=0.350      P=0.105N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/89 (1%)    1/60 (2%)    1/60 (2%)    1/130 (1%) |  0/60 (0%)    0/60 (0%)    0/60 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   3.6%         5.9%         9.1%         9.1%      |   0.0%         0.0%         0.0%         6.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     1/11 (9%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    2/30 (7%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      673          631          729 (T)   |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.395      P=0.552      P=0.347      P=0.541    |  P=0.037 *      (e)          (e)        P=0.245    |
|INCIDENTAL TUMOR       |  P=0.570      P=0.772      P=0.743      P=0.541    |  P=0.037 *      (e)          (e)        P=0.245    |
|LOGISTIC REGRESSION    |  P=0.514      P=0.663      P=0.558      P=0.541    |  P=0.037 *      (e)          (e)        P=0.245    |
|COCHRAN-ARMITAGE       |  P=0.469N                                          |  P=0.046 *                                         |
|FISHER EXACT           |               P=0.645      P=0.645      P=0.649N   |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  10
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/89 (1%)    1/60 (2%)    1/60 (2%)    1/130 (1%) |  0/60 (0%)    0/60 (0%)    0/60 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   3.6%         5.9%         9.1%         9.1%      |   0.0%         0.0%         0.0%         6.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     1/11 (9%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    2/30 (7%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      673          631          729 (T)   |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.395      P=0.552      P=0.347      P=0.541    |  P=0.037 *      (e)          (e)        P=0.245    |
|INCIDENTAL TUMOR       |  P=0.570      P=0.772      P=0.743      P=0.541    |  P=0.037 *      (e)          (e)        P=0.245    |
|LOGISTIC REGRESSION    |  P=0.514      P=0.663      P=0.558      P=0.541    |  P=0.037 *      (e)          (e)        P=0.245    |
|COCHRAN-ARMITAGE       |  P=0.469N                                          |  P=0.046 *                                         |
|FISHER EXACT           |               P=0.645      P=0.645      P=0.649N   |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/86 (1%)    2/59 (3%)    3/59 (5%)    1/128 (1%) |  0/59 (0%)    0/59 (0%)    0/58 (0%)    0/56 (0%)  |
|ADJUSTED (b)           |   3.6%        13.2%        13.5%         9.1%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    1/9 (11%)    0/2 (0%)     1/11 (9%)  |  0/29 (0%)    0/38 (0%)    0/35 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      518          548          729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.470      P=0.255      P=0.060      P=0.541    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.423N     P=0.255      P=0.452      P=0.541    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.518N     P=0.411      P=0.154      P=0.541    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.363N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.361      P=0.184      P=0.643N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  11
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pharynx                                                                                                                          |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/89 (1%)    1/60 (2%)    1/60 (2%)    0/130 (0%) |  0/60 (0%)    0/60 (0%)    0/60 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   3.6%         5.9%         9.1%         0.0%      |   0.0%         0.0%         0.0%         6.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    2/30 (7%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      673          631          ---       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.498N     P=0.552      P=0.347      P=0.686N   |  P=0.037 *      (e)          (e)        P=0.245    |
|INCIDENTAL TUMOR       |  P=0.295N     P=0.772      P=0.743      P=0.686N   |  P=0.037 *      (e)          (e)        P=0.245    |
|LOGISTIC REGRESSION    |  P=0.373N     P=0.663      P=0.558      P=0.688N   |  P=0.037 *      (e)          (e)        P=0.245    |
|COCHRAN-ARMITAGE       |  P=0.222N                                          |  P=0.046 *                                         |
|FISHER EXACT           |               P=0.645      P=0.645      P=0.406N   |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 21/88 (24%)  12/58 (21%)  18/58 (31%)  19/130 (15%)| 30/59 (51%)  26/57 (46%)  23/58 (40%)  28/59 (47%) |
|ADJUSTED (b)           |  52.8%        56.2%       100.0%        54.2%      |  74.2%        61.6%        60.2%        69.1%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  1/17 (6%)    0/10 (0%)    2/9 (22%)    4/20 (20%) |  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           | 11/28 (39%)   3/9 (33%)    2/2 (100%)   4/11 (36%) | 19/29 (66%)  21/37 (57%)  20/35 (57%)  18/30 (60%) |
|FIRST INCIDENCE (DAYS) |   337          577          455 (I)      453 (I)   |   435          456 (I)      622          463       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.120      P=0.432      P<0.001 **   P=0.275    |  P=0.485N     P=0.064N     P=0.033N*    P=0.393N   |
|INCIDENTAL TUMOR       |  P=0.108N     P=0.101N     P=0.540      P=0.115N   |  P=0.347N     P=0.380N     P=0.184N     P=0.342N   |
|LOGISTIC REGRESSION    |  P=0.211N     P=0.222N     P=0.208      P=0.171N   |  P=0.364N     P=0.250N     P=0.125N     P=0.407N   |
|COCHRAN-ARMITAGE       |  P=0.050N*                                         |  P=0.401N                                          |
|FISHER EXACT           |               P=0.406N     P=0.221      P=0.061N   |               P=0.353N     P=0.151N     P=0.427N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  12
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 21/88 (24%)  12/58 (21%)  18/58 (31%)  19/130 (15%)| 31/59 (53%)  26/57 (46%)  23/58 (40%)  28/59 (47%) |
|ADJUSTED (b)           |  52.8%        56.2%       100.0%        54.2%      |  75.0%        61.6%        60.2%        69.1%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  1/17 (6%)    0/10 (0%)    2/9 (22%)    4/20 (20%) |  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           | 11/28 (39%)   3/9 (33%)    2/2 (100%)   4/11 (36%) | 19/29 (66%)  21/37 (57%)  20/35 (57%)  18/30 (60%) |
|FIRST INCIDENCE (DAYS) |   337          577          455 (I)      453 (I)   |   435          456 (I)      622          463       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.120      P=0.432      P<0.001 **   P=0.275    |  P=0.427N     P=0.046N*    P=0.023N*    P=0.336N   |
|INCIDENTAL TUMOR       |  P=0.108N     P=0.101N     P=0.540      P=0.115N   |  P=0.288N     P=0.330N     P=0.159N     P=0.276N   |
|LOGISTIC REGRESSION    |  P=0.211N     P=0.222N     P=0.208      P=0.171N   |  P=0.298N     P=0.189N     P=0.087N     P=0.329N   |
|COCHRAN-ARMITAGE       |  P=0.050N*                                         |  P=0.343N                                          |
|FISHER EXACT           |               P=0.406N     P=0.221      P=0.061N   |               P=0.288N     P=0.113N     P=0.356N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/89 (1%)    4/60 (7%)    1/60 (2%)    1/130 (1%) |  1/60 (2%)    1/60 (2%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   2.6%        28.1%        50.0%         1.4%      |   2.8%         2.6%         0.0%         3.3%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    2/9 (22%)    1/2 (50%)    0/11 (0%)  |  0/29 (0%)    1/38 (3%)    0/36 (0%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   609          569          729 (T)      511       |   693          729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.565N     P=0.053      P=0.421      P=0.711N   |  P=0.636N     P=0.718N     P=0.489N     P=0.755    |
|INCIDENTAL TUMOR       |  P=0.323N     P=0.160      P=0.743      P=0.395N   |  P=0.621N     P=0.729      P=0.757N     P=0.754    |
|LOGISTIC REGRESSION    |  P=0.362N     P=0.107      P=0.591      P=0.691N   |  P=0.625N     P=0.745N     P=0.498N     P=0.762N   |
|COCHRAN-ARMITAGE       |  P=0.213N                                          |  P=0.616N                                          |
|FISHER EXACT           |               P=0.085      P=0.645      P=0.649N   |               P=0.752N     P=0.500N     P=0.752N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  13
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/89 (1%)    4/60 (7%)    0/60 (0%)    1/130 (1%) |  0/60 (0%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   2.6%        28.1%         0.0%         1.4%      |   0.0%         2.6%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    2/9 (22%)    0/2 (0%)     0/11 (0%)  |  0/29 (0%)    1/38 (3%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   609          569          ---          511       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.481N     P=0.053      P=0.643N     P=0.711N   |  P=0.576N     P=0.554        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.231N     P=0.160      P=0.274N     P=0.395N   |  P=0.576N     P=0.554        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.300N     P=0.107      P=0.586N     P=0.691N   |  P=0.576N     P=0.554        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.200N                                          |  P=0.567N                                          |
|FISHER EXACT           |               P=0.085      P=0.597N     P=0.649N   |               P=0.500        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/89 (2%)    5/60 (8%)    1/60 (2%)    2/130 (2%) |  1/60 (2%)    1/60 (2%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   6.0%        29.6%        50.0%         2.4%      |   2.8%         2.6%         0.0%         3.3%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    2/9 (22%)    1/2 (50%)    0/11 (0%)  |  0/29 (0%)    1/38 (3%)    0/36 (0%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   609          482          729 (T)      380       |   693          729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.530N     P=0.058      P=0.473      P=0.696N   |  P=0.636N     P=0.718N     P=0.489N     P=0.755    |
|INCIDENTAL TUMOR       |  P=0.249N     P=0.147      P=0.761      P=0.381N   |  P=0.621N     P=0.729      P=0.757N     P=0.754    |
|LOGISTIC REGRESSION    |  P=0.267N     P=0.127      P=0.676      P=0.575N   |  P=0.625N     P=0.745N     P=0.498N     P=0.762N   |
|COCHRAN-ARMITAGE       |  P=0.184N                                          |  P=0.616N                                          |
|FISHER EXACT           |               P=0.094      P=0.645N     P=0.537N   |               P=0.752N     P=0.500N     P=0.752N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  14
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/89 (2%)    0/60 (0%)    1/60 (2%)    0/130 (0%) |  0/60 (0%)    1/60 (2%)    1/60 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |   6.0%         0.0%         2.8%         0.0%      |   0.0%         2.6%         2.8%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    1/38 (3%)    1/36 (3%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   609          ---          539          ---       |   ---          729 (T)      729 (T)      679       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.254N     P=0.367N     P=0.685      P=0.338N   |  P=0.371      P=0.554      P=0.543      P=0.500    |
|INCIDENTAL TUMOR       |  P=0.101N     P=0.269N     P=0.441N     P=0.148N   |  P=0.379      P=0.554      P=0.543      P=0.481    |
|LOGISTIC REGRESSION    |  P=0.169N     P=0.303N     P=0.667N     P=0.244N   |  P=0.378      P=0.554      P=0.543      P=0.504    |
|COCHRAN-ARMITAGE       |  P=0.132N                                          |  P=0.384                                           |
|FISHER EXACT           |               P=0.355N     P=0.645N     P=0.164N   |               P=0.500      P=0.500      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/89 (3%)    0/60 (0%)    1/60 (2%)    0/130 (0%) |  0/60 (0%)    1/60 (2%)    1/60 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |   9.5%         0.0%         2.8%         0.0%      |   0.0%         2.6%         2.8%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  2/28 (7%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    1/38 (3%)    1/36 (3%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   609          ---          539          ---       |   ---          729 (T)      729 (T)      679       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.175N     P=0.275N     P=0.706      P=0.241N   |  P=0.371      P=0.554      P=0.543      P=0.500    |
|INCIDENTAL TUMOR       |  P=0.071N     P=0.202N     P=0.407N     P=0.111N   |  P=0.379      P=0.554      P=0.543      P=0.481    |
|LOGISTIC REGRESSION    |  P=0.095N     P=0.187N     P=0.542N     P=0.151N   |  P=0.378      P=0.554      P=0.543      P=0.504    |
|COCHRAN-ARMITAGE       |  P=0.056N                                          |  P=0.384                                           |
|FISHER EXACT           |               P=0.210N     P=0.469N     P=0.066N   |               P=0.500      P=0.500      P=0.500    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  15
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/89 (0%)    2/60 (3%)    0/60 (0%)    2/130 (2%) |  1/60 (2%)    3/60 (5%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%        12.8%         0.0%         3.0%      |   3.4%         7.9%         0.0%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    1/10 (10%)   0/9 (0%)     1/20 (5%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    1/9 (11%)    0/2 (0%)     0/11 (0%)  |  1/29 (3%)    3/38 (8%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          455 (I)      ---          453 (I)   |   729 (T)      729 (T)      ---          543       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.255      P=0.085        (e)        P=0.280    |  P=0.413N     P=0.406      P=0.457N     P=0.752N   |
|INCIDENTAL TUMOR       |  P=0.323      P=0.085        (e)        P=0.418    |  P=0.362N     P=0.406      P=0.457N     P=0.682N   |
|LOGISTIC REGRESSION    |  P=0.393      P=0.172        (e)        P=0.323    |  P=0.408N     P=0.406      P=0.457N     P=0.762    |
|COCHRAN-ARMITAGE       |  P=0.411                                           |  P=0.409N                                          |
|FISHER EXACT           |               P=0.161        (e)        P=0.351    |               P=0.309      P=0.500N     P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 53/85 (62%)  52/59 (88%)  50/55 (91%)  98/130 (75%)|                                                    |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          1/18 (6%)  |                                                    |
|INTERIM SACRIFICE 2 (c)| 15/17 (88%)   9/10 (90%)   8/9 (89%)   18/20 (90%) |                                                    |
|TERMINAL (d)           | 28/28 (100%)  9/9 (100%)   2/2 (100%)  11/11 (100%)|                                                    |
|FIRST INCIDENCE (DAYS) |   408          453 (I)      428          275 (I)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |                                                    |
|INCIDENTAL TUMOR       |  P=0.002 **   P=0.091      P=0.008 **   P=0.001 ** |                                                    |
|LOGISTIC REGRESSION    |  P=0.029 *    P=0.306      P=0.171      P=0.037 *  |                                                    |
|COCHRAN-ARMITAGE       |  P=0.151                                           |                                                    |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P=0.030 *  |                                                    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  16
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/87 (2%)    1/59 (2%)    1/58 (2%)    0/130 (0%) |  0/59 (0%)    0/60 (0%)    0/59 (0%)    2/59 (3%)  |
|ADJUSTED (b)           |   6.3%         3.3%         5.3%         0.0%      |   0.0%         0.0%         0.0%         6.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/35 (0%)    2/30 (7%)  |
|FIRST INCIDENCE (DAYS) |   660          631          615          ---       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.294N     P=0.687N     P=0.532      P=0.426N   |  P=0.038 *      (e)          (e)        P=0.245    |
|INCIDENTAL TUMOR       |  P=0.081N     P=0.418N     P=0.587N     P=0.269N   |  P=0.038 *      (e)          (e)        P=0.245    |
|LOGISTIC REGRESSION    |  P=0.166N     P=0.600N     P=0.743      P=0.289N   |  P=0.038 *      (e)          (e)        P=0.245    |
|COCHRAN-ARMITAGE       |  P=0.096N                                          |  P=0.046 *                                         |
|FISHER EXACT           |               P=0.643N     P=0.649N     P=0.160N   |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/87 (1%)    3/59 (5%)    0/58 (0%)    0/130 (0%) |  0/59 (0%)    0/60 (0%)    0/59 (0%)    1/59 (2%)  |
|ADJUSTED (b)           |   1.2%        13.6%         0.0%         0.0%      |   0.0%         0.0%         0.0%         2.5%      |
|INTERIM SACRIFICE 1 (c)|  1/17 (6%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/35 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   274 (I)      645          ---          ---       |   ---          ---          ---          651       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.268N     P=0.055        (e)        P=0.489N   |  P=0.195        (e)          (e)        P=0.505    |
|INCIDENTAL TUMOR       |  P=0.144N     P=0.364        (e)        P=0.489N   |  P=0.230        (e)          (e)        P=0.481    |
|LOGISTIC REGRESSION    |  P=0.101N     P=0.189      P=0.751N     P=0.403N   |  P=0.199        (e)          (e)        P=0.501    |
|COCHRAN-ARMITAGE       |  P=0.096N                                          |  P=0.198                                           |
|FISHER EXACT           |               P=0.181      P=0.600N     P=0.401N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  17
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/87 (2%)    4/59 (7%)    0/58 (0%)    1/130 (1%) |  1/59 (2%)    1/60 (2%)    1/59 (2%)    2/59 (3%)  |
|ADJUSTED (b)           |   4.7%        22.3%         0.0%         2.2%      |   2.3%         2.6%         2.9%         5.8%      |
|INTERIM SACRIFICE 1 (c)|  1/17 (6%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    1/38 (3%)    1/35 (3%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   274 (I)      645          ---          588       |   607          729 (T)      729 (T)      651       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.392N     P=0.037 *    P=0.959N     P=0.580N   |  P=0.340      P=0.728N     P=0.742N     P=0.509    |
|INCIDENTAL TUMOR       |  P=0.171N     P=0.389      P=0.959N     P=0.425N   |  P=0.380      P=0.647      P=0.719N     P=0.514    |
|LOGISTIC REGRESSION    |  P=0.140N     P=0.227      P=0.342N     P=0.369N   |  P=0.350      P=0.756N     P=0.757      P=0.504    |
|COCHRAN-ARMITAGE       |  P=0.101N                                          |  P=0.349                                           |
|FISHER EXACT           |               P=0.180      P=0.358N     P=0.353N   |               P=0.748N     P=0.752N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  8/60 (13%)  14/60 (23%)   6/60 (10%)   7/60 (12%) |
|ADJUSTED (b)           |                                                    |  23.7%        34.4%        14.4%        18.6%      |
|INTERIM SACRIFICE 1 (c)|                                                    |                                                    |
|INTERIM SACRIFICE 2 (c)|                                                    |  1/10 (10%)   1/10 (10%)   2/10 (20%)   2/10 (20%) |
|TERMINAL (d)           |                                                    |  5/29 (17%)  12/38 (32%)   4/36 (11%)   3/30 (10%) |
|FIRST INCIDENCE (DAYS) |                                                    |   455 (I)      456 (I)      455 (I)      456 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.241N     P=0.275      P=0.276N     P=0.500N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.238N     P=0.191      P=0.405N     P=0.506N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.213N     P=0.144      P=0.394N     P=0.485N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.220N                                          |
|FISHER EXACT           |                                                    |               P=0.119      P=0.389N     P=0.500N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  18
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/89 (0%)    2/60 (3%)    0/60 (0%)    1/130 (1%) |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         6.8%         0.0%         1.5%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          482          ---          512       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.561      P=0.192        (e)        P=0.587    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.518N     P=0.338        (e)        P=0.791    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.626N     P=0.164        (e)        P=0.575    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.611N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.161        (e)        P=0.594    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/89 (9%)   10/60 (17%)   1/60 (2%)   10/130 (8%) |  6/60 (10%)   5/60 (8%)    6/60 (10%)   4/60 (7%)  |
|ADJUSTED (b)           |  21.9%        46.4%         3.6%        43.7%      |  15.5%        11.6%        14.4%         9.1%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     1/20 (5%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  3/28 (11%)   2/9 (22%)    0/2 (0%)     3/11 (27%) |  1/29 (3%)    3/38 (8%)    2/36 (6%)    1/30 (3%)  |
|FIRST INCIDENCE (DAYS) |   420          503          580          453 (I)   |   554          439          554          375       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.157      P=0.057      P=0.404N     P=0.095    |  P=0.355N     P=0.401N     P=0.559N     P=0.371N   |
|INCIDENTAL TUMOR       |  P=0.377N     P=0.566      P=0.020N*    P=0.586N   |  P=0.187N     P=0.504      P=0.428      P=0.265N   |
|LOGISTIC REGRESSION    |  P=0.520N     P=0.199      P=0.093N     P=0.468    |  P=0.241N     P=0.619      P=0.456      P=0.378N   |
|COCHRAN-ARMITAGE       |  P=0.210N                                          |  P=0.336N                                          |
|FISHER EXACT           |               P=0.125      P=0.062N     P=0.458N   |               P=0.500N     P=0.619N     P=0.372N   |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  19
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/89 (1%)    0/60 (0%)    1/60 (2%)    2/130 (2%) |  1/60 (2%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   2.7%         0.0%         5.9%         7.5%      |   2.6%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     0/20 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/9 (0%)     0/2 (0%)     0/11 (0%)  |  0/29 (0%)    0/38 (0%)    0/36 (0%)    0/30 (0%)  |
|FIRST INCIDENCE (DAYS) |   622          ---          622          583       |   662          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.191      P=0.523N     P=0.579      P=0.415    |  P=0.310N     P=0.485N     P=0.495N     P=0.505N   |
|INCIDENTAL TUMOR       |  P=0.546      P=0.375N     P=0.490N     P=0.637N   |  P=0.334N     P=0.621N     P=0.757N     P=0.519N   |
|LOGISTIC REGRESSION    |  P=0.320      P=0.554N     P=0.659      P=0.558    |  P=0.305N     P=0.496N     P=0.502N     P=0.497N   |
|COCHRAN-ARMITAGE       |  P=0.411                                           |  P=0.306N                                          |
|FISHER EXACT           |               P=0.597N     P=0.645      P=0.639    |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 63/89 (71%)  55/60 (92%)  54/60 (90%) 101/130 (78%)| 38/60 (63%)  45/60 (75%)  38/60 (63%)  42/60 (70%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  86.0%        93.7%        90.3%        87.3%      |
|INTERIM SACRIFICE 1 (c)|  1/17 (6%)    0/0          0/0          1/18 (6%)  |                                                    |
|INTERIM SACRIFICE 2 (c)| 16/17 (94%)   9/10 (90%)   8/9 (89%)   19/20 (95%) |  1/10 (10%)   2/10 (20%)   2/10 (20%)   2/10 (20%) |
|TERMINAL (d)           | 28/28 (100%)  9/9 (100%)   2/2 (100%)  11/11 (100%)| 23/29 (79%)  35/38 (92%)  32/36 (89%)  24/30 (80%) |
|FIRST INCIDENCE (DAYS) |   274 (I)      453 (I)      428          275 (I)   |   435          456 (I)      455 (I)      456 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.303      P=0.443N     P=0.161N     P=0.358    |
|INCIDENTAL TUMOR       |  P=0.102      P=0.469      P=0.355      P=0.156    |  P=0.524      P=0.079      P=0.410      P=0.431    |
|LOGISTIC REGRESSION    |  P=0.231      P=0.605N     P=0.414N     P=0.280    |  P=0.450      P=0.113      P=0.594      P=0.339    |
|COCHRAN-ARMITAGE       |  P=0.425                                           |  P=0.399                                           |
|FISHER EXACT           |               P=0.001 **   P=0.004 **   P=0.159    |               P=0.118      P=0.575N     P=0.281    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  20
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/KG      25 MG/KG     50 MG/KG     100MG/KG  |   VEHICLE      25 MG/KG     50 MG/KG     100MG/KG  |
|                       |   65 KILL                                65 STOP   |   CONTROL                                          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 17/89 (19%)  13/60 (22%)   4/60 (7%)   19/130 (15%)| 10/60 (17%)   7/60 (12%)  10/60 (17%)  11/60 (18%) |
|ADJUSTED (b)           |  45.6%        51.5%        53.8%        68.2%      |  24.9%        16.7%        24.4%        29.7%      |
|INTERIM SACRIFICE 1 (c)|  0/17 (0%)    0/0          0/0          0/18 (0%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/17 (0%)    0/10 (0%)    0/9 (0%)     1/20 (5%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  9/28 (32%)   2/9 (22%)    1/2 (50%)    6/11 (55%) |  2/29 (7%)    5/38 (13%)   6/36 (17%)   7/30 (23%) |
|FIRST INCIDENCE (DAYS) |   420          482          408          253       |   554          439          554          375       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.063      P=0.198      P=0.614      P=0.050 *  |  P=0.310      P=0.202N     P=0.491N     P=0.507    |
|INCIDENTAL TUMOR       |  P=0.396N     P=0.216N     P=0.014N*    P=0.479N   |  P=0.496      P=0.594N     P=0.386      P=0.595N   |
|LOGISTIC REGRESSION    |  P=0.481N     P=0.555N     P=0.057N     P=0.580N   |  P=0.434      P=0.448N     P=0.420      P=0.518    |
|COCHRAN-ARMITAGE       |  P=0.151N                                          |  P=0.338                                           |
|FISHER EXACT           |               P=0.428      P=0.026N*    P=0.243N   |               P=0.301N     P=0.596N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 64/89 (72%)  55/60 (92%)  55/60 (92%) 103/130 (79%)| 42/60 (70%)  46/60 (77%)  42/60 (70%)  45/60 (75%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  89.2%        93.8%        91.2%        89.8%      |
|INTERIM SACRIFICE 1 (c)|  1/17 (6%)    0/0          0/0          1/18 (6%)  |                                                    |
|INTERIM SACRIFICE 2 (c)| 16/17 (94%)   9/10 (90%)   8/9 (89%)   20/20 (100%)|  1/10 (10%)   2/10 (20%)   2/10 (20%)   2/10 (20%) |
|TERMINAL (d)           | 28/28 (100%)  9/9 (100%)   2/2 (100%)  11/11 (100%)| 24/29 (83%)  35/38 (92%)  32/36 (89%)  25/30 (83%) |
|FIRST INCIDENCE (DAYS) |   274 (I)      453 (I)      408          253       |   435          439          455 (I)      375       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.313      P=0.250N     P=0.176N     P=0.427    |
|INCIDENTAL TUMOR       |  P=0.076      P=0.638      P=0.529      P=0.137    |  P=0.431N     P=0.123      P=0.335      P=0.588    |
|LOGISTIC REGRESSION    |  P=0.147      P=0.489N     P=0.514N     P=0.195    |  P=0.541N     P=0.164      P=0.495      P=0.435    |
|COCHRAN-ARMITAGE       |  P=0.367                                           |  P=0.394                                           |
|FISHER EXACT           |               P=0.002 **   P=0.002 **   P=0.138    |               P=0.268      P=0.579N     P=0.342    |
|=================================================================================================================================|
         DATE: 09/12/94                     EXPERIMENT: 05090 TEST: 01                                                 PAGE  21
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- COUMARIN
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   274  453
          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).