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TDMS Study 05067-10 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                   THEOPHYLLINE                                     DATE: 07/03/96       
EXPERIMENT: 05067 TEST: 10                                                                                     TIME: 12:40:28       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-05297                              ROUTE: GAVAGE                                                  NTP C#: 61609D       
PATHOLOGIST: ROGER THOMPSON                                                                                    CAS: 58-55-9         
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                                                             CORE STUDY                                                             
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                   THEOPHYLLINE                                     DATE: 07/03/96       
EXPERIMENT: 05067 TEST: 10                                                                                     TIME: 12:40:28       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-05297                              ROUTE: GAVAGE                                                  NTP C#: 61609D       
PATHOLOGIST: ROGER THOMPSON                                                                                    CAS: 58-55-9         


                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                                    
                                                    ----------------
                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                   THEOPHYLLINE                                     DATE: 07/03/96       
EXPERIMENT: 05067 TEST: 10                                                                                     TIME: 12:40:28       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-05297                              ROUTE: GAVAGE                                                  NTP C#: 61609D       
PATHOLOGIST: ROGER THOMPSON                                                                                    CAS: 58-55-9         


                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                          IN THE ANALYSIS OF THE STUDY OF THEOPHYLLINE
              ====================================================================================================
                                                           MALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Liver                         Hepatocellular Adenoma
                                            Hepatocellular Carcinoma
                                            Hepatocellular Carcinoma or Hepatocellular Adenoma
                                            Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
              Lung                          Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
              All Organs                    Hemangiosarcoma
                                            Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated
                                             Cell Type
                                            Benign Tumors
                                            Malignant Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
                                                           FEMALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Liver                         Hepatocellular Adenoma
                                            Hepatocellular Carcinoma or Hepatocellular Adenoma
                                            Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
              All Organs                    Histiocytic Sarcoma
                                            Benign Tumors
                                            Malignant Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   1
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/50 (8%)    2/50 (4%)    1/50 (2%)    1/49 (2%)  |  1/49 (2%)    0/50 (0%)    0/50 (0%)    1/49 (2%)  |
|ADJUSTED (b)           |  11.1%         5.7%         2.3%         3.8%      |   2.8%         0.0%         0.0%         3.0%      |
|TERMINAL (d)           |  4/36 (11%)   2/35 (6%)    1/44 (2%)    1/26 (4%)  |  1/36 (3%)    0/37 (0%)    0/34 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   725 (T)      725 (T)      725 (T)      725 (T)   |   725 (T)      ---          ---          725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.255N     P=0.349N     P=0.124N     P=0.288N   |  P=0.514      P=0.495N     P=0.511N     P=0.742    |
|INCIDENTAL TUMOR       |  P=0.255N     P=0.349N     P=0.124N     P=0.288N   |  P=0.514      P=0.495N     P=0.511N     P=0.742    |
|LOGISTIC REGRESSION    |  P=0.255N     P=0.349N     P=0.124N     P=0.288N   |  P=0.514      P=0.495N     P=0.511N     P=0.742    |
|COCHRAN-ARMITAGE       |  P=0.182N                                          |  P=0.534                                           |
|FISHER EXACT           |               P=0.339N     P=0.181N     P=0.187N   |               P=0.495N     P=0.495N     P=0.753N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/49 (0%)    1/50 (2%)    0/49 (0%)    0/49 (0%)  |  1/50 (2%)    2/48 (4%)    2/50 (4%)    1/49 (2%)  |
|ADJUSTED (b)           |   0.0%         2.9%         0.0%         0.0%      |   2.7%         5.4%         5.9%         3.0%      |
|TERMINAL (d)           |  0/35 (0%)    1/35 (3%)    0/44 (0%)    0/26 (0%)  |  1/37 (3%)    2/37 (5%)    2/34 (6%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          725 (T)      ---          ---       |   725 (T)      725 (T)      725 (T)      725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.631N     P=0.500        (e)          (e)      |  P=0.567N     P=0.500      P=0.470      P=0.736    |
|INCIDENTAL TUMOR       |  P=0.631N     P=0.500        (e)          (e)      |  P=0.567N     P=0.500      P=0.470      P=0.736    |
|LOGISTIC REGRESSION    |  P=0.631N     P=0.500        (e)          (e)      |  P=0.567N     P=0.500      P=0.470      P=0.736    |
|COCHRAN-ARMITAGE       |  P=0.578N                                          |  P=0.523N                                          |
|FISHER EXACT           |               P=0.505        (e)          (e)      |               P=0.485      P=0.500      P=0.747    |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   2
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    1/50 (2%)    0/50 (0%)    0/49 (0%)  |  0/50 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   4.9%         2.1%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/36 (3%)    0/35 (0%)    0/44 (0%)    0/26 (0%)  |  0/37 (0%)    0/37 (0%)    0/34 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   635          511          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.216N     P=0.520N     P=0.213N     P=0.327N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.182N     P=0.364N     P=0.270N     P=0.380N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.097N     P=0.412N     P=0.266N     P=0.297N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.172N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.500N     P=0.247N     P=0.253N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    3/50 (6%)    2/50 (4%)    2/50 (4%)  |  6/50 (12%)   5/50 (10%)   4/50 (8%)    2/50 (4%)  |
|ADJUSTED (b)           |   2.4%         8.6%         4.5%         6.7%      |  15.3%        12.7%        10.5%         6.1%      |
|TERMINAL (d)           |  0/36 (0%)    3/35 (9%)    2/44 (5%)    1/26 (4%)  |  4/37 (11%)   4/37 (11%)   2/34 (6%)    2/33 (6%)  |
|FIRST INCIDENCE (DAYS) |   700          725 (T)      725 (T)      407       |   654          603          688          725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.440      P=0.288      P=0.554      P=0.369    |  P=0.135N     P=0.497N     P=0.382N     P=0.164N   |
|INCIDENTAL TUMOR       |  P=0.464      P=0.228      P=0.452      P=0.390    |  P=0.091N     P=0.471N     P=0.126N     P=0.088N   |
|LOGISTIC REGRESSION    |  P=0.513      P=0.275      P=0.519      P=0.522    |  P=0.117N     P=0.496N     P=0.093N     P=0.147N   |
|COCHRAN-ARMITAGE       |  P=0.586                                           |  P=0.105N                                          |
|FISHER EXACT           |               P=0.309      P=0.500      P=0.500    |               P=0.500N     P=0.370N     P=0.134N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   3
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         5.1%         0.0%      |
|TERMINAL (d)           |  0/36 (0%)    0/35 (0%)    0/44 (0%)    0/26 (0%)  |  0/37 (0%)    0/37 (0%)    1/34 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          661          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.710N       (e)        P=0.249        (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.646N       (e)        P=0.365        (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.699N       (e)        P=0.229        (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.697N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.247        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    3/50 (6%)    2/50 (4%)    2/50 (4%)  |  6/50 (12%)   5/50 (10%)   6/50 (12%)   2/50 (4%)  |
|ADJUSTED (b)           |   2.4%         8.6%         4.5%         6.7%      |  15.3%        12.7%        15.3%         6.1%      |
|TERMINAL (d)           |  0/36 (0%)    3/35 (9%)    2/44 (5%)    1/26 (4%)  |  4/37 (11%)   4/37 (11%)   3/34 (9%)    2/33 (6%)  |
|FIRST INCIDENCE (DAYS) |   700          725 (T)      725 (T)      407       |   654          603          661          725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.440      P=0.288      P=0.554      P=0.369    |  P=0.143N     P=0.497N     P=0.614      P=0.164N   |
|INCIDENTAL TUMOR       |  P=0.464      P=0.228      P=0.452      P=0.390    |  P=0.087N     P=0.471N     P=0.281N     P=0.088N   |
|LOGISTIC REGRESSION    |  P=0.513      P=0.275      P=0.519      P=0.522    |  P=0.124N     P=0.496N     P=0.264N     P=0.147N   |
|COCHRAN-ARMITAGE       |  P=0.586                                           |  P=0.111N                                          |
|FISHER EXACT           |               P=0.309      P=0.500      P=0.500    |               P=0.500N     P=0.620N     P=0.134N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   4
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    3/50 (6%)    1/50 (2%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   4.9%         8.3%         2.3%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/36 (3%)    2/35 (6%)    1/44 (2%)    0/26 (0%)  |  0/37 (0%)    0/37 (0%)    0/34 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   635          711          725 (T)      ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.146N     P=0.477      P=0.449N     P=0.327N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.193N     P=0.450      P=0.512N     P=0.335N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.151N     P=0.479      P=0.525N     P=0.292N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.104N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.500      P=0.500N     P=0.247N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 21/50 (42%)  18/50 (36%)  12/50 (24%)   2/50 (4%)  | 20/50 (40%)  11/50 (22%)  12/50 (24%)   3/50 (6%)  |
|ADJUSTED (b)           |  52.1%        48.1%        26.6%         7.7%      |  48.3%        29.7%        34.0%         9.1%      |
|TERMINAL (d)           | 17/36 (47%)  16/35 (46%)  11/44 (25%)   2/26 (8%)  | 16/37 (43%)  11/37 (30%)  11/34 (32%)   3/33 (9%)  |
|FIRST INCIDENCE (DAYS) |   605          521          668          725 (T)   |   624          725 (T)      669          725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.396N     P=0.011N*    P<0.001N** |  P<0.001N**   P=0.042N*    P=0.098N     P<0.001N** |
|INCIDENTAL TUMOR       |  P<0.001N**   P=0.363N     P=0.026N*    P<0.001N** |  P<0.001N**   P=0.044N*    P=0.158N     P<0.001N** |
|LOGISTIC REGRESSION    |  P<0.001N**   P=0.447N     P=0.030N*    P<0.001N** |  P<0.001N**   P=0.035N*    P=0.049N*    P<0.001N** |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.341N     P=0.044N*    P<0.001N** |               P=0.041N*    P=0.066N     P<0.001N** |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   5
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 19/50 (38%)  14/50 (28%)  12/50 (24%)   2/50 (4%)  | 11/50 (22%)   5/50 (10%)   6/50 (12%)   5/50 (10%) |
|ADJUSTED (b)           |  42.0%        32.2%        26.0%         7.2%      |  26.0%        11.8%        15.3%        14.6%      |
|TERMINAL (d)           | 11/36 (31%)   7/35 (20%)  10/44 (23%)   1/26 (4%)  |  7/37 (19%)   2/37 (5%)    3/34 (9%)    4/33 (12%) |
|FIRST INCIDENCE (DAYS) |   485          464          556          636       |   501          591          667          704       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.001N**   P=0.279N     P=0.050N     P=0.002N** |  P=0.217N     P=0.095N     P=0.164N     P=0.129N   |
|INCIDENTAL TUMOR       |  P=0.001N**   P=0.164N     P=0.170N     P=0.001N** |  P=0.150N     P=0.088N     P=0.084N     P=0.083N   |
|LOGISTIC REGRESSION    |  P=0.002N**   P=0.129N     P=0.137N     P=0.001N** |  P=0.156N     P=0.090N     P=0.171N     P=0.092N   |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.164N                                          |
|FISHER EXACT           |               P=0.198N     P=0.097N     P<0.001N** |               P=0.086N     P=0.143N     P=0.086N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 34/50 (68%)  27/50 (54%)  22/50 (44%)   4/50 (8%)  | 29/50 (58%)  14/50 (28%)  18/50 (36%)   8/50 (16%) |
|ADJUSTED (b)           |  72.1%        62.2%        46.7%        14.6%      |  64.1%        34.5%        46.7%        23.4%      |
|TERMINAL (d)           | 23/36 (64%)  19/35 (54%)  19/44 (43%)   3/26 (12%) | 21/37 (57%)  11/37 (30%)  14/34 (41%)   7/33 (21%) |
|FIRST INCIDENCE (DAYS) |   485          464          556          636       |   501          591          667          704       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.221N     P=0.004N**   P<0.001N** |  P=0.002N**   P=0.005N**   P=0.050N*    P<0.001N** |
|INCIDENTAL TUMOR       |  P<0.001N**   P=0.123N     P=0.021N*    P<0.001N** |  P<0.001N**   P=0.003N**   P=0.040N*    P<0.001N** |
|LOGISTIC REGRESSION    |  P<0.001N**   P=0.113N     P=0.016N*    P<0.001N** |  P<0.001N**   P=0.002N**   P=0.020N*    P<0.001N** |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.109N     P=0.013N*    P<0.001N** |               P=0.002N**   P=0.022N*    P<0.001N** |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   6
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 34/50 (68%)  27/50 (54%)  22/50 (44%)   4/50 (8%)  | 29/50 (58%)  14/50 (28%)  18/50 (36%)   8/50 (16%) |
|ADJUSTED (b)           |  72.1%        62.2%        46.7%        14.6%      |  64.1%        34.5%        46.7%        23.4%      |
|TERMINAL (d)           | 23/36 (64%)  19/35 (54%)  19/44 (43%)   3/26 (12%) | 21/37 (57%)  11/37 (30%)  14/34 (41%)   7/33 (21%) |
|FIRST INCIDENCE (DAYS) |   485          464          556          636       |   501          591          667          704       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.221N     P=0.004N**   P<0.001N** |  P=0.002N**   P=0.005N**   P=0.050N*    P<0.001N** |
|INCIDENTAL TUMOR       |  P<0.001N**   P=0.123N     P=0.021N*    P<0.001N** |  P<0.001N**   P=0.003N**   P=0.040N*    P<0.001N** |
|LOGISTIC REGRESSION    |  P<0.001N**   P=0.113N     P=0.016N*    P<0.001N** |  P<0.001N**   P=0.002N**   P=0.020N*    P<0.001N** |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.109N     P=0.013N*    P<0.001N** |               P=0.002N**   P=0.022N*    P<0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/50 (16%)   8/50 (16%)  10/50 (20%)   4/50 (8%)  |  3/50 (6%)    4/50 (8%)    4/50 (8%)    3/50 (6%)  |
|ADJUSTED (b)           |  22.2%        22.0%        22.7%        14.6%      |   7.6%         9.7%        10.8%         9.1%      |
|TERMINAL (d)           |  8/36 (22%)   7/35 (20%)  10/44 (23%)   3/26 (12%) |  2/37 (5%)    2/37 (5%)    3/34 (9%)    3/33 (9%)  |
|FIRST INCIDENCE (DAYS) |   725 (T)      633          725 (T)      636       |   642          611          655          725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.300N     P=0.580      P=0.585      P=0.372N   |  P=0.567N     P=0.502      P=0.485      P=0.614    |
|INCIDENTAL TUMOR       |  P=0.317N     P=0.605      P=0.585      P=0.378N   |  P=0.556      P=0.472      P=0.482      P=0.556    |
|LOGISTIC REGRESSION    |  P=0.366N     P=0.534      P=0.585      P=0.441N   |  P=0.533N     P=0.494      P=0.505      P=0.645    |
|COCHRAN-ARMITAGE       |  P=0.123N                                          |  P=0.514N                                          |
|FISHER EXACT           |               P=0.607N     P=0.398      P=0.178N   |               P=0.500      P=0.500      P=0.661N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   7
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/50 (12%)   1/50 (2%)    5/50 (10%)   1/50 (2%)  |  1/50 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |  15.9%         2.9%        11.0%         3.8%      |   2.7%         2.0%         0.0%         0.0%      |
|TERMINAL (d)           |  5/36 (14%)   1/35 (3%)    4/44 (9%)    1/26 (4%)  |  1/37 (3%)    0/37 (0%)    0/34 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   700          725 (T)      620          725 (T)   |   725 (T)      584          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.221N     P=0.066N     P=0.383N     P=0.131N   |  P=0.321N     P=0.753N     P=0.517N     P=0.523N   |
|INCIDENTAL TUMOR       |  P=0.261N     P=0.082N     P=0.468N     P=0.172N   |  P=0.388N     P=0.747      P=0.517N     P=0.523N   |
|LOGISTIC REGRESSION    |  P=0.246N     P=0.071N     P=0.477N     P=0.148N   |  P=0.249N     P=0.755      P=0.517N     P=0.523N   |
|COCHRAN-ARMITAGE       |  P=0.126N                                          |  P=0.303N                                          |
|FISHER EXACT           |               P=0.056N     P=0.500N     P=0.056N   |               P=0.753N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/50 (26%)   9/50 (18%)  15/50 (30%)   5/50 (10%) |  4/50 (8%)    5/50 (10%)   4/50 (8%)    3/50 (6%)  |
|ADJUSTED (b)           |  34.9%        24.8%        33.2%        18.3%      |  10.2%        11.6%        10.8%         9.1%      |
|TERMINAL (d)           | 12/36 (33%)   8/35 (23%)  14/44 (32%)   4/26 (15%) |  3/37 (8%)    2/37 (5%)    3/34 (9%)    3/33 (9%)  |
|FIRST INCIDENCE (DAYS) |   700          633          620          636       |   642          584          655          725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.172N     P=0.262N     P=0.532N     P=0.139N   |  P=0.408N     P=0.506      P=0.623      P=0.557N   |
|INCIDENTAL TUMOR       |  P=0.205N     P=0.270N     P=0.585      P=0.173N   |  P=0.498N     P=0.467      P=0.626      P=0.613N   |
|LOGISTIC REGRESSION    |  P=0.231N     P=0.306N     P=0.512      P=0.189N   |  P=0.355N     P=0.489      P=0.634N     P=0.522N   |
|COCHRAN-ARMITAGE       |  P=0.045N*                                         |  P=0.352N                                          |
|FISHER EXACT           |               P=0.235N     P=0.412      P=0.033N*  |               P=0.500      P=0.643N     P=0.500N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   8
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/49 (0%)    0/50 (0%)    0/48 (0%)    0/44 (0%)  |  9/49 (18%)   7/45 (16%)   7/50 (14%)   5/48 (10%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  24.1%        19.4%        20.6%        15.6%      |
|TERMINAL (d)           |  0/36 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)  |  8/36 (22%)   7/36 (19%)   7/34 (21%)   5/32 (16%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   643          725 (T)      725 (T)      725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.261N     P=0.391N     P=0.432N     P=0.257N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.278N     P=0.421N     P=0.492N     P=0.293N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.209N     P=0.391N     P=0.340N     P=0.207N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.183N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.466N     P=0.376N     P=0.205N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    1/50 (2%)    0/50 (0%)  |  2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         4.9%         2.0%         0.0%      |   5.2%         0.0%         2.6%         0.0%      |
|TERMINAL (d)           |  0/36 (0%)    0/35 (0%)    0/44 (0%)    0/26 (0%)  |  1/37 (3%)    0/37 (0%)    0/34 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          627          577          ---       |   655          ---          704          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.480N     P=0.217      P=0.504        (e)      |  P=0.279N     P=0.237N     P=0.488N     P=0.247N   |
|INCIDENTAL TUMOR       |  P=0.629N     P=0.180      P=0.398        (e)      |  P=0.177N     P=0.208N     P=0.217N     P=0.148N   |
|LOGISTIC REGRESSION    |  P=0.305N     P=0.258      P=0.305        (e)      |  P=0.271N     P=0.239N     P=0.509N     P=0.240N   |
|COCHRAN-ARMITAGE       |  P=0.378N                                          |  P=0.271N                                          |
|FISHER EXACT           |               P=0.247      P=0.500        (e)      |               P=0.247N     P=0.500N     P=0.247N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE   9
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    1/50 (2%)    0/50 (0%)  |  2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         4.9%         2.0%         0.0%      |   5.2%         0.0%         2.6%         0.0%      |
|TERMINAL (d)           |  0/36 (0%)    0/35 (0%)    0/44 (0%)    0/26 (0%)  |  1/37 (3%)    0/37 (0%)    0/34 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          627          577          ---       |   655          ---          704          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.480N     P=0.217      P=0.504        (e)      |  P=0.279N     P=0.237N     P=0.488N     P=0.247N   |
|INCIDENTAL TUMOR       |  P=0.629N     P=0.180      P=0.398        (e)      |  P=0.177N     P=0.208N     P=0.217N     P=0.148N   |
|LOGISTIC REGRESSION    |  P=0.305N     P=0.258      P=0.305        (e)      |  P=0.271N     P=0.239N     P=0.509N     P=0.240N   |
|COCHRAN-ARMITAGE       |  P=0.378N                                          |  P=0.271N                                          |
|FISHER EXACT           |               P=0.247      P=0.500        (e)      |               P=0.247N     P=0.500N     P=0.247N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    1/49 (2%)    0/50 (0%)    0/49 (0%)  |  0/50 (0%)    2/50 (4%)    0/49 (0%)    0/48 (0%)  |
|ADJUSTED (b)           |   4.9%         2.9%         0.0%         0.0%      |   0.0%         4.7%         0.0%         0.0%      |
|TERMINAL (d)           |  1/36 (3%)    1/35 (3%)    0/44 (0%)    0/26 (0%)  |  0/37 (0%)    1/37 (3%)    0/34 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   635          725 (T)      ---          ---       |   ---          591          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.207N     P=0.523N     P=0.213N     P=0.327N   |  P=0.389N     P=0.244        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.226N     P=0.468N     P=0.270N     P=0.335N   |  P=0.487N     P=0.227        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.194N     P=0.509N     P=0.266N     P=0.294N   |  P=0.328N     P=0.228        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.171N                                          |  P=0.377N                                          |
|FISHER EXACT           |               P=0.508N     P=0.247N     P=0.253N   |               P=0.247        (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE  10
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    4/50 (8%)    1/50 (2%)    1/50 (2%)  |  4/50 (8%)    2/50 (4%)    2/50 (4%)    2/50 (4%)  |
|ADJUSTED (b)           |   2.8%        11.4%         2.3%         3.8%      |  10.8%         5.4%         5.9%         5.3%      |
|TERMINAL (d)           |  1/36 (3%)    4/35 (11%)   1/44 (2%)    1/26 (4%)  |  4/37 (11%)   2/37 (5%)    2/34 (6%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   725 (T)      725 (T)      725 (T)      725 (T)   |   725 (T)      725 (T)      725 (T)      627       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.445N     P=0.170      P=0.716N     P=0.688    |  P=0.426N     P=0.336N     P=0.376N     P=0.384N   |
|INCIDENTAL TUMOR       |  P=0.445N     P=0.170      P=0.716N     P=0.688    |  P=0.463N     P=0.336N     P=0.376N     P=0.444N   |
|LOGISTIC REGRESSION    |  P=0.445N     P=0.170      P=0.716N     P=0.688    |  P=0.395N     P=0.336N     P=0.376N     P=0.356N   |
|COCHRAN-ARMITAGE       |  P=0.331N                                          |  P=0.375N                                          |
|FISHER EXACT           |               P=0.181      P=0.753N     P=0.753N   |               P=0.339N     P=0.339N     P=0.339N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    4/50 (8%)    0/50 (0%)    1/50 (2%)  |  4/50 (8%)    2/50 (4%)    2/50 (4%)    2/50 (4%)  |
|ADJUSTED (b)           |   2.8%        11.4%         0.0%         3.8%      |  10.8%         5.4%         5.9%         5.3%      |
|TERMINAL (d)           |  1/36 (3%)    4/35 (11%)   0/44 (0%)    1/26 (4%)  |  4/37 (11%)   2/37 (5%)    2/34 (6%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   725 (T)      725 (T)      ---          725 (T)   |   725 (T)      725 (T)      725 (T)      627       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.431N     P=0.170      P=0.460N     P=0.688    |  P=0.426N     P=0.336N     P=0.376N     P=0.384N   |
|INCIDENTAL TUMOR       |  P=0.431N     P=0.170      P=0.460N     P=0.688    |  P=0.463N     P=0.336N     P=0.376N     P=0.444N   |
|LOGISTIC REGRESSION    |  P=0.431N     P=0.170      P=0.460N     P=0.688    |  P=0.395N     P=0.336N     P=0.376N     P=0.356N   |
|COCHRAN-ARMITAGE       |  P=0.329N                                          |  P=0.375N                                          |
|FISHER EXACT           |               P=0.181      P=0.500N     P=0.753N   |               P=0.339N     P=0.339N     P=0.339N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE  11
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)  |  4/50 (8%)    2/50 (4%)    3/50 (6%)    1/50 (2%)  |
|ADJUSTED (b)           |   0.0%         2.9%         0.0%         7.2%      |  10.8%         5.4%         8.8%         3.0%      |
|TERMINAL (d)           |  0/36 (0%)    1/35 (3%)    0/44 (0%)    1/26 (4%)  |  4/37 (11%)   2/37 (5%)    3/34 (9%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          725 (T)      ---          636       |   725 (T)      725 (T)      725 (T)      725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.086      P=0.494        (e)        P=0.165    |  P=0.229N     P=0.336N     P=0.547N     P=0.214N   |
|INCIDENTAL TUMOR       |  P=0.073      P=0.494        (e)        P=0.154    |  P=0.229N     P=0.336N     P=0.547N     P=0.214N   |
|LOGISTIC REGRESSION    |  P=0.091      P=0.494        (e)        P=0.170    |  P=0.229N     P=0.336N     P=0.547N     P=0.214N   |
|COCHRAN-ARMITAGE       |  P=0.151                                           |  P=0.191N                                          |
|FISHER EXACT           |               P=0.500        (e)        P=0.247    |               P=0.339N     P=0.500N     P=0.181N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    0/50 (0%)    2/50 (4%)  |  4/50 (8%)    2/50 (4%)    3/50 (6%)    1/50 (2%)  |
|ADJUSTED (b)           |   0.0%         5.7%         0.0%         7.2%      |  10.8%         5.4%         8.8%         3.0%      |
|TERMINAL (d)           |  0/36 (0%)    2/35 (6%)    0/44 (0%)    1/26 (4%)  |  4/37 (11%)   2/37 (5%)    3/34 (9%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          725 (T)      ---          636       |   725 (T)      725 (T)      725 (T)      725 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.189      P=0.232        (e)        P=0.165    |  P=0.229N     P=0.336N     P=0.547N     P=0.214N   |
|INCIDENTAL TUMOR       |  P=0.170      P=0.232        (e)        P=0.154    |  P=0.229N     P=0.336N     P=0.547N     P=0.214N   |
|LOGISTIC REGRESSION    |  P=0.187      P=0.232        (e)        P=0.170    |  P=0.229N     P=0.336N     P=0.547N     P=0.214N   |
|COCHRAN-ARMITAGE       |  P=0.287                                           |  P=0.191N                                          |
|FISHER EXACT           |               P=0.247        (e)        P=0.247    |               P=0.339N     P=0.500N     P=0.181N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE  12
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/50 (4%)    0/50 (0%)    1/50 (2%)    1/50 (2%)  |
|ADJUSTED (b)           |                                                    |   5.4%         0.0%         2.9%         2.9%      |
|TERMINAL (d)           |                                                    |  2/37 (5%)    0/37 (0%)    1/34 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   725 (T)      ---          725 (T)      705       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.650N     P=0.238N     P=0.530N     P=0.533N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.597N     P=0.238N     P=0.530N     P=0.419N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.633N     P=0.238N     P=0.530N     P=0.512N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.619N                                          |
|FISHER EXACT           |                                                    |               P=0.247N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    5/50 (10%)   2/50 (4%)    0/50 (0%)  |  0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   7.7%        13.0%         4.5%         0.0%      |   0.0%         4.7%         0.0%         0.0%      |
|TERMINAL (d)           |  2/36 (6%)    3/35 (9%)    2/44 (5%)    0/26 (0%)  |  0/37 (0%)    1/37 (3%)    0/34 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   635          511          725 (T)      ---       |   ---          591          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.072N     P=0.339      P=0.424N     P=0.194N   |  P=0.389N     P=0.244        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.073N     P=0.373      P=0.473N     P=0.199N   |  P=0.463N     P=0.227        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.058N     P=0.368      P=0.501N     P=0.182N   |  P=0.318N     P=0.228        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.041N*                                         |  P=0.369N                                          |
|FISHER EXACT           |               P=0.357      P=0.500N     P=0.121N   |               P=0.247        (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE  13
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)  |  1/50 (2%)    8/50 (16%)   4/50 (8%)    2/50 (4%)  |
|ADJUSTED (b)           |   2.0%         2.3%         2.3%         0.0%      |   2.7%        18.2%        10.4%         5.8%      |
|TERMINAL (d)           |  0/36 (0%)    0/35 (0%)    1/44 (2%)    0/26 (0%)  |  1/37 (3%)    3/37 (8%)    1/34 (3%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   485          569          725 (T)      ---       |   725 (T)      603          696          705       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.411N     P=0.746      P=0.736N     P=0.598N   |  P=0.305N     P=0.023 *    P=0.179      P=0.467    |
|INCIDENTAL TUMOR       |  P=0.325N     P=0.619N     P=0.540      P=0.282N   |  P=0.269N     P=0.016 *    P=0.441      P=0.581    |
|LOGISTIC REGRESSION    |  P=0.171N     P=0.650N     P=0.628      P=0.344N   |  P=0.252N     P=0.016 *    P=0.189      P=0.488    |
|COCHRAN-ARMITAGE       |  P=0.323N                                          |  P=0.266N                                          |
|FISHER EXACT           |               P=0.753N     P=0.753N     P=0.500N   |               P=0.015 *    P=0.181      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated                                               |
|     Cell Type                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/50 (10%)   3/50 (6%)    5/50 (10%)   1/50 (2%)  | 11/50 (22%)   8/50 (16%)  10/50 (20%)   8/50 (16%) |
|ADJUSTED (b)           |  12.0%         7.9%        10.8%         2.8%      |  26.6%        21.1%        24.3%        20.4%      |
|TERMINAL (d)           |  3/36 (8%)    2/35 (6%)    3/44 (7%)    0/26 (0%)  |  8/37 (22%)   7/37 (19%)   5/34 (15%)   4/33 (12%) |
|FIRST INCIDENCE (DAYS) |   438          562          668          382       |   555          702          593          578       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.219N     P=0.378N     P=0.540N     P=0.212N   |  P=0.445N     P=0.307N     P=0.526N     P=0.385N   |
|INCIDENTAL TUMOR       |  P=0.162N     P=0.231N     P=0.326      P=0.028N*  |  P=0.428N     P=0.310N     P=0.515N     P=0.468N   |
|LOGISTIC REGRESSION    |  P=0.056N     P=0.245N     P=0.470      P=0.041N*  |  P=0.368N     P=0.302N     P=0.541N     P=0.306N   |
|COCHRAN-ARMITAGE       |  P=0.111N                                          |  P=0.356N                                          |
|FISHER EXACT           |               P=0.357N     P=0.630N     P=0.102N   |               P=0.306N     P=0.500N     P=0.306N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE  14
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 29/50 (58%)  29/50 (58%)  22/50 (44%)   9/50 (18%) | 33/50 (66%)  27/50 (54%)  27/50 (54%)  18/50 (36%) |
|ADJUSTED (b)           |  70.4%        76.0%        48.8%        31.5%      |  76.6%        67.2%        70.6%        49.6%      |
|TERMINAL (d)           | 24/36 (67%)  26/35 (74%)  21/44 (48%)   7/26 (27%) | 27/37 (73%)  24/37 (65%)  23/34 (68%)  15/33 (45%) |
|FIRST INCIDENCE (DAYS) |   605          521          668          407       |   624          603          655          627       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.494      P=0.017N*    P=0.004N** |  P=0.013N*    P=0.158N     P=0.252N     P=0.012N*  |
|INCIDENTAL TUMOR       |  P<0.001N**   P=0.517      P=0.042N*    P=0.004N** |  P=0.010N**   P=0.150N     P=0.156N     P=0.007N** |
|LOGISTIC REGRESSION    |  P<0.001N**   P=0.380      P=0.058N     P=0.005N** |  P=0.004N**   P=0.123N     P=0.079N     P=0.003N** |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.003N**                                        |
|FISHER EXACT           |               P=0.580N     P=0.115N     P<0.001N** |               P=0.154N     P=0.154N     P=0.002N** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/50 (64%)  24/50 (48%)  25/50 (50%)   4/50 (8%)  | 26/50 (52%)  24/50 (48%)  22/50 (44%)  17/50 (34%) |
|ADJUSTED (b)           |  66.2%        50.5%        50.0%        13.4%      |  56.0%        48.7%        48.3%        41.1%      |
|TERMINAL (d)           | 20/36 (56%)  12/35 (34%)  19/44 (43%)   2/26 (8%)  | 17/37 (46%)  12/37 (32%)  11/34 (32%)   9/33 (27%) |
|FIRST INCIDENCE (DAYS) |   438          421          556          382       |   501          494          593          578       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.190N     P=0.047N*    P<0.001N** |  P=0.126N     P=0.424N     P=0.342N     P=0.140N   |
|INCIDENTAL TUMOR       |  P<0.001N**   P=0.046N*    P=0.280N     P<0.001N** |  P=0.044N*    P=0.425N     P=0.175N     P=0.053N   |
|LOGISTIC REGRESSION    |  P<0.001N**   P=0.029N*    P=0.262N     P<0.001N** |  P=0.103N     P=0.445N     P=0.335N     P=0.059N   |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.039N*                                         |
|FISHER EXACT           |               P=0.079N     P=0.113N     P<0.001N** |               P=0.421N     P=0.274N     P=0.053N   |
|=================================================================================================================================|
         DATE: 07/03/96                     EXPERIMENT: 05067 TEST: 10                                                 PAGE  15
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      15 MG/KG     50 MG/KG     150       |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL                                MG/KG     |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 44/50 (88%)  42/50 (84%)  38/50 (76%)  13/50 (26%) | 46/50 (92%)  39/50 (78%)  41/50 (82%)  28/50 (56%) |
|ADJUSTED (b)           |  89.7%        87.4%        76.0%        42.6%      |  92.0%        79.5%        87.1%        66.6%      |
|TERMINAL (d)           | 31/36 (86%)  29/35 (83%)  32/44 (73%)   9/26 (35%) | 33/37 (89%)  27/37 (73%)  28/34 (82%)  19/33 (58%) |
|FIRST INCIDENCE (DAYS) |   438          421          556          382       |   501          494          593          578       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.555N     P=0.019N*    P<0.001N** |  P=0.014N*    P=0.154N     P=0.343N     P=0.010N*  |
|INCIDENTAL TUMOR       |  P<0.001N**   P=0.362N     P=0.164N     P<0.001N** |  P<0.001N**   P=0.049N*    P=0.097N     P<0.001N** |
|LOGISTIC REGRESSION    |  P<0.001N**   P=0.348N     P=0.164N     P<0.001N** |  P<0.001N**   P=0.046N*    P=0.118N     P<0.001N** |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.387N     P=0.096N     P<0.001N** |               P=0.045N*    P=0.117N     P<0.001N** |
|=================================================================================================================================|
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).