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TDMS Study 05067-09 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                   THEOPHYLLINE                                     DATE: 07/11/96       
EXPERIMENT: 05067 TEST: 09                                                                                     TIME: 17:25:22       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-05297                              ROUTE: GAVAGE                                                  NTP C#: 61609D       
PATHOLOGIST: DANIEL FARNELL                  FARNELL, DANIEL R.                                                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: 07/11/96       
EXPERIMENT: 05067 TEST: 09                                                                                     TIME: 17:25:22       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-05297                              ROUTE: GAVAGE                                                  NTP C#: 61609D       
PATHOLOGIST: DANIEL FARNELL                  FARNELL, DANIEL R.                                                CAS: 58-55-9         


                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                                    
                                                    ----------------
                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Clitoral/Preputial Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                   THEOPHYLLINE                                     DATE: 07/11/96       
EXPERIMENT: 05067 TEST: 09                                                                                     TIME: 17:25:22       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-05297                              ROUTE: GAVAGE                                                  NTP C#: 61609D       
PATHOLOGIST: DANIEL FARNELL                  FARNELL, DANIEL R.                                                CAS: 58-55-9         


                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                          IN THE ANALYSIS OF THE STUDY OF THEOPHYLLINE
              ====================================================================================================
                                                           MALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Adrenal Medulla               Pheochromocytoma Benign
              Pancreas                      Adenoma
              Pituitary Gland: Pars Distalis or Unspecified Site
                                            Adenoma
              Skin                          Fibroma
              Testes                        Adenoma
              All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated
                                            Benign Tumors
                                            Malignant Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
                                                           FEMALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Mammary Gland                 Fibroadenoma
                                            Fibroma, Fibroadenoma, Carcinoma, or Adenoma
              Pituitary Gland: Pars Distalis or Unspecified Site
                                            Adenoma
              All Organs                    Benign Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   1
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/50 (14%)   5/49 (10%)   7/50 (14%)  10/50 (20%) |  2/50 (4%)    0/49 (0%)    0/50 (0%)    1/49 (2%)  |
|ADJUSTED (b)           |  25.7%        15.1%        24.1%        36.1%      |   5.1%         0.0%         0.0%         3.0%      |
|TERMINAL (d)           |  5/23 (22%)   4/32 (13%)   7/29 (24%)   7/24 (29%) |  0/32 (0%)    0/30 (0%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   598          723          729 (T)      457       |   576          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.070      P=0.206N     P=0.467N     P=0.283    |  P=0.635N     P=0.238N     P=0.237N     P=0.485N   |
|INCIDENTAL TUMOR       |  P=0.058      P=0.304N     P=0.510N     P=0.201    |  P=0.653N     P=0.150N     P=0.208N     P=0.454N   |
|LOGISTIC REGRESSION    |  P=0.043 *    P=0.320N     P=0.616N     P=0.163    |  P=0.650N     P=0.233N     P=0.260N     P=0.504N   |
|COCHRAN-ARMITAGE       |  P=0.143                                           |  P=0.654N                                          |
|FISHER EXACT           |               P=0.394N     P=0.613N     P=0.298    |               P=0.253N     P=0.247N     P=0.508N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    2/49 (4%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/49 (0%)    0/50 (0%)    0/49 (0%)  |
|ADJUSTED (b)           |   4.3%         5.2%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    1/32 (3%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      500          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.236N     P=0.571      P=0.454N     P=0.492N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.151N     P=0.518      P=0.454N     P=0.492N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.198N     P=0.495      P=0.454N     P=0.492N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.208N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.492      P=0.500N     P=0.500N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   2
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/50 (16%)   7/49 (14%)   7/50 (14%)  10/50 (20%) |  3/50 (6%)    0/49 (0%)    0/50 (0%)    1/49 (2%)  |
|ADJUSTED (b)           |  29.8%        19.8%        24.1%        36.1%      |   8.1%         0.0%         0.0%         3.0%      |
|TERMINAL (d)           |  6/23 (26%)   5/32 (16%)   7/29 (24%)   7/24 (29%) |  1/32 (3%)    0/30 (0%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   598          500          729 (T)      457       |   576          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.159      P=0.292N     P=0.342N     P=0.384    |  P=0.433N     P=0.127N     P=0.121N     P=0.294N   |
|INCIDENTAL TUMOR       |  P=0.169      P=0.420N     P=0.381N     P=0.293    |  P=0.447N     P=0.079N     P=0.106N     P=0.269N   |
|LOGISTIC REGRESSION    |  P=0.115      P=0.480N     P=0.496N     P=0.234    |  P=0.452N     P=0.122N     P=0.126N     P=0.313N   |
|COCHRAN-ARMITAGE       |  P=0.278                                           |  P=0.452N                                          |
|FISHER EXACT           |               P=0.517N     P=0.500N     P=0.398    |               P=0.125N     P=0.121N     P=0.316N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/49 (4%)    0/50 (0%)    0/49 (0%)  |  1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         5.0%         0.0%         0.0%      |   2.1%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    1/33 (3%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          372          ---          ---       |   498          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.386N     P=0.277        (e)          (e)      |  P=0.482N     P=0.508N     P=0.496N     P=0.513N   |
|INCIDENTAL TUMOR       |  P=0.276N     P=0.219        (e)          (e)      |  P=0.626N     P=0.669N     P=0.567N     P=0.748N   |
|LOGISTIC REGRESSION    |  P=0.261N     P=0.273        (e)          (e)      |  P=0.468N     P=0.409N     P=0.680N     P=0.392N   |
|COCHRAN-ARMITAGE       |  P=0.371N                                          |  P=0.474N                                          |
|FISHER EXACT           |               P=0.242        (e)          (e)      |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   3
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/49 (4%)    4/50 (8%)    3/50 (6%)  |  4/49 (8%)    3/50 (6%)    1/50 (2%)    1/50 (2%)  |
|ADJUSTED (b)           |   0.0%         5.6%        11.6%        12.5%      |  11.7%         8.6%         2.6%         3.0%      |
|TERMINAL (d)           |  0/23 (0%)    1/32 (3%)    2/29 (7%)    3/24 (13%) |  3/32 (9%)    1/30 (3%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          666          498          729 (T)   |   667          614          670          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.137      P=0.299      P=0.081      P=0.126    |  P=0.127N     P=0.532N     P=0.179N     P=0.175N   |
|INCIDENTAL TUMOR       |  P=0.150      P=0.196      P=0.055      P=0.126    |  P=0.128N     P=0.449N     P=0.159N     P=0.174N   |
|LOGISTIC REGRESSION    |  P=0.139      P=0.240      P=0.065      P=0.126    |  P=0.131N     P=0.507N     P=0.167N     P=0.172N   |
|COCHRAN-ARMITAGE       |  P=0.200                                           |  P=0.132N                                          |
|FISHER EXACT           |               P=0.242      P=0.059      P=0.121    |               P=0.489N     P=0.175N     P=0.175N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    2/49 (4%)    0/50 (0%)    4/50 (8%)  |  0/49 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   8.9%         6.3%         0.0%        13.7%      |   0.0%         5.4%         0.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    2/32 (6%)    0/29 (0%)    2/24 (8%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   572          729 (T)      ---          498       |   ---          595          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.207      P=0.402N     P=0.125N     P=0.423    |  P=0.362N     P=0.237        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.224      P=0.596N     P=0.241N     P=0.357    |  P=0.370N     P=0.342        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.278      P=0.508N     P=0.111N     P=0.508    |  P=0.365N     P=0.249        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.291                                           |  P=0.367N                                          |
|FISHER EXACT           |               P=0.510N     P=0.121N     P=0.500    |               P=0.253        (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   4
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    4/49 (8%)    4/50 (8%)    7/50 (14%) |  4/49 (8%)    5/50 (10%)   1/50 (2%)    1/50 (2%)  |
|ADJUSTED (b)           |   8.9%        11.7%        11.6%        25.4%      |  11.7%        13.6%         2.6%         3.0%      |
|TERMINAL (d)           |  0/23 (0%)    3/32 (9%)    2/29 (7%)    5/24 (21%) |  3/32 (9%)    1/30 (3%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   572          666          498          498       |   667          595          670          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.056      P=0.622      P=0.533      P=0.131    |  P=0.075N     P=0.470      P=0.179N     P=0.175N   |
|INCIDENTAL TUMOR       |  P=0.064      P=0.391      P=0.348      P=0.096    |  P=0.073N     P=0.610      P=0.159N     P=0.174N   |
|LOGISTIC REGRESSION    |  P=0.076      P=0.494      P=0.516      P=0.118    |  P=0.076N     P=0.500      P=0.167N     P=0.172N   |
|COCHRAN-ARMITAGE       |  P=0.111                                           |  P=0.077N                                          |
|FISHER EXACT           |               P=0.489      P=0.500      P=0.159    |               P=0.513      P=0.175N     P=0.175N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    1/50 (2%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    1/49 (2%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |  11.9%         3.0%         0.0%         0.0%      |   0.0%         2.9%         0.0%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    1/33 (3%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   726          729 (T)      ---          ---       |   ---          670          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.109N     P=0.203N     P=0.095N     P=0.126N   |  P=0.571N     P=0.484        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.157N     P=0.357N     P=0.209N     P=0.255N   |  P=0.591N     P=0.473        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.114N     P=0.211N     P=0.102N     P=0.132N   |  P=0.573N     P=0.497        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.097N                                          |  P=0.575N                                          |
|FISHER EXACT           |               P=0.309N     P=0.121N     P=0.121N   |               P=0.495        (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   5
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    1/50 (2%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    2/49 (4%)    0/50 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |  11.9%         3.0%         0.0%         0.0%      |   0.0%         6.1%         0.0%         3.0%      |
|TERMINAL (d)           |  1/23 (4%)    1/33 (3%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    1/30 (3%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   726          729 (T)      ---          ---       |   ---          670          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.109N     P=0.203N     P=0.095N     P=0.126N   |  P=0.634      P=0.224        (e)        P=0.506    |
|INCIDENTAL TUMOR       |  P=0.157N     P=0.357N     P=0.209N     P=0.255N   |  P=0.625      P=0.218        (e)        P=0.506    |
|LOGISTIC REGRESSION    |  P=0.114N     P=0.211N     P=0.102N     P=0.132N   |  P=0.627      P=0.230        (e)        P=0.506    |
|COCHRAN-ARMITAGE       |  P=0.097N                                          |  P=0.624                                           |
|FISHER EXACT           |               P=0.309N     P=0.121N     P=0.121N   |               P=0.242        (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    2/50 (4%)    0/50 (0%)    1/50 (2%)  |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   6.4%         6.1%         0.0%         3.2%      |   0.0%         0.0%         3.0%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    2/33 (6%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   546          729 (T)      ---          595       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.447N     P=0.594N     P=0.221N     P=0.567N   |  P=0.777N       (e)        P=0.506        (e)      |
|INCIDENTAL TUMOR       |  P=0.338N     P=0.644N     P=0.196N     P=0.439N   |  P=0.777N       (e)        P=0.506        (e)      |
|LOGISTIC REGRESSION    |  P=0.396N     P=0.693N     P=0.220N     P=0.468N   |  P=0.777N       (e)        P=0.506        (e)      |
|COCHRAN-ARMITAGE       |  P=0.382N                                          |  P=0.786N                                          |
|FISHER EXACT           |               P=0.691N     P=0.247N     P=0.500N   |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   6
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    0/50 (0%)    1/50 (2%)    2/50 (4%)  |  0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |   6.6%         0.0%         3.4%         8.3%      |   0.0%         3.3%         0.0%         3.0%      |
|TERMINAL (d)           |  1/23 (4%)    0/33 (0%)    1/29 (3%)    2/24 (8%)  |  0/32 (0%)    1/30 (3%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   614          ---          729 (T)      729 (T)   |   ---          729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.340      P=0.198N     P=0.458N     P=0.676    |  P=0.477      P=0.487        (e)        P=0.506    |
|INCIDENTAL TUMOR       |  P=0.349      P=0.236N     P=0.459N     P=0.675    |  P=0.477      P=0.487        (e)        P=0.506    |
|LOGISTIC REGRESSION    |  P=0.322      P=0.238N     P=0.509N     P=0.628    |  P=0.477      P=0.487        (e)        P=0.506    |
|COCHRAN-ARMITAGE       |  P=0.404                                           |  P=0.464                                           |
|FISHER EXACT           |               P=0.247N     P=0.500N     P=0.691N   |               P=0.500        (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    0/50 (0%)    1/50 (2%)    2/50 (4%)  |  0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |  10.9%         0.0%         3.4%         8.3%      |   0.0%         3.3%         0.0%         3.0%      |
|TERMINAL (d)           |  2/23 (9%)    0/33 (0%)    1/29 (3%)    2/24 (8%)  |  0/32 (0%)    1/30 (3%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   614          ---          729 (T)      729 (T)   |   ---          729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.501      P=0.082N     P=0.254N     P=0.515N   |  P=0.477      P=0.487        (e)        P=0.506    |
|INCIDENTAL TUMOR       |  P=0.509      P=0.099N     P=0.255N     P=0.517N   |  P=0.477      P=0.487        (e)        P=0.506    |
|LOGISTIC REGRESSION    |  P=0.473      P=0.116N     P=0.312N     P=0.585N   |  P=0.477      P=0.487        (e)        P=0.506    |
|COCHRAN-ARMITAGE       |  P=0.563                                           |  P=0.464                                           |
|FISHER EXACT           |               P=0.121N     P=0.309N     P=0.500N   |               P=0.500        (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   7
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    2/50 (4%)    1/50 (2%)    1/50 (2%)  | 22/50 (44%)  19/50 (38%)  12/50 (24%)  12/50 (24%) |
|ADJUSTED (b)           |  10.2%         6.1%         3.4%         4.2%      |  54.4%        53.6%        32.2%        31.6%      |
|TERMINAL (d)           |  0/23 (0%)    2/33 (6%)    1/29 (3%)    1/24 (4%)  | 14/32 (44%)  14/30 (47%)   9/33 (27%)   8/33 (24%) |
|FIRST INCIDENCE (DAYS) |   670          729 (T)      729 (T)      729 (T)   |   498          614          498          393       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.314N     P=0.382N     P=0.271N     P=0.334N   |  P=0.022N*    P=0.452N     P=0.033N*    P=0.036N*  |
|INCIDENTAL TUMOR       |  P=0.420N     P=0.622N     P=0.527N     P=0.610N   |  P=0.030N*    P=0.407N     P=0.029N*    P=0.055N   |
|LOGISTIC REGRESSION    |  P=0.341N     P=0.466N     P=0.313N     P=0.372N   |  P=0.023N*    P=0.391N     P=0.025N*    P=0.030N*  |
|COCHRAN-ARMITAGE       |  P=0.263N                                          |  P=0.025N*                                         |
|FISHER EXACT           |               P=0.500N     P=0.309N     P=0.309N   |               P=0.342N     P=0.028N*    P=0.028N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    2/50 (4%)    1/50 (2%)    1/50 (2%)  | 23/50 (46%)  20/50 (40%)  12/50 (24%)  12/50 (24%) |
|ADJUSTED (b)           |  10.2%         6.1%         3.4%         4.2%      |  57.0%        55.0%        32.2%        31.6%      |
|TERMINAL (d)           |  0/23 (0%)    2/33 (6%)    1/29 (3%)    1/24 (4%)  | 15/32 (47%)  14/30 (47%)   9/33 (27%)   8/33 (24%) |
|FIRST INCIDENCE (DAYS) |   670          729 (T)      729 (T)      729 (T)   |   498          614          498          393       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.314N     P=0.382N     P=0.271N     P=0.334N   |  P=0.013N*    P=0.456N     P=0.021N*    P=0.024N*  |
|INCIDENTAL TUMOR       |  P=0.420N     P=0.622N     P=0.527N     P=0.610N   |  P=0.017N*    P=0.415N     P=0.018N*    P=0.035N*  |
|LOGISTIC REGRESSION    |  P=0.341N     P=0.466N     P=0.313N     P=0.372N   |  P=0.013N*    P=0.394N     P=0.015N*    P=0.019N*  |
|COCHRAN-ARMITAGE       |  P=0.263N                                          |  P=0.015N*                                         |
|FISHER EXACT           |               P=0.500N     P=0.309N     P=0.309N   |               P=0.343N     P=0.018N*    P=0.018N*  |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   8
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)                                                                       |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |   5.8%         0.0%         3.4%         0.0%      |   0.0%         0.0%         0.0%         3.0%      |
|TERMINAL (d)           |  0/23 (0%)    0/33 (0%)    1/29 (3%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   617          ---          729 (T)      ---       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.312N     P=0.214N     P=0.479N     P=0.284N   |  P=0.223        (e)          (e)        P=0.506    |
|INCIDENTAL TUMOR       |  P=0.358N     P=0.360N     P=0.582N     P=0.403N   |  P=0.223        (e)          (e)        P=0.506    |
|LOGISTIC REGRESSION    |  P=0.284N     P=0.234N     P=0.503N     P=0.231N   |  P=0.223        (e)          (e)        P=0.506    |
|COCHRAN-ARMITAGE       |  P=0.271N                                          |  P=0.214                                           |
|FISHER EXACT           |               P=0.247N     P=0.500N     P=0.247N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)                                                                       |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |  1/50 (2%)    0/50 (0%)    1/50 (2%)    1/50 (2%)  |
|ADJUSTED (b)           |   5.8%         0.0%         3.4%         0.0%      |   2.0%         0.0%         2.9%         3.0%      |
|TERMINAL (d)           |  0/23 (0%)    0/33 (0%)    1/29 (3%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   617          ---          729 (T)      ---       |   399          ---          723          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.312N     P=0.214N     P=0.479N     P=0.284N   |  P=0.548      P=0.508N     P=0.754N     P=0.755    |
|INCIDENTAL TUMOR       |  P=0.358N     P=0.360N     P=0.582N     P=0.403N   |  P=0.466      P=0.669N     P=0.724      P=0.638    |
|LOGISTIC REGRESSION    |  P=0.284N     P=0.234N     P=0.503N     P=0.231N   |  P=0.552      P=0.333N     P=0.685      P=0.716N   |
|COCHRAN-ARMITAGE       |  P=0.271N                                          |  P=0.545                                           |
|FISHER EXACT           |               P=0.247N     P=0.500N     P=0.247N   |               P=0.500N     P=0.753N     P=0.753N   |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE   9
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/50 (20%)   7/50 (14%)   4/50 (8%)    4/50 (8%)  |  1/50 (2%)    1/48 (2%)    0/49 (0%)    2/50 (4%)  |
|ADJUSTED (b)           |  38.6%        20.5%        13.8%        15.4%      |   3.1%         3.4%         0.0%         6.1%      |
|TERMINAL (d)           |  8/23 (35%)   6/33 (18%)   4/29 (14%)   3/24 (13%) |  1/32 (3%)    1/29 (3%)    0/32 (0%)    2/33 (6%)  |
|FIRST INCIDENCE (DAYS) |   649          719          729 (T)      642       |   729 (T)      729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.115N     P=0.096N     P=0.029N*    P=0.073N   |  P=0.356      P=0.740      P=0.500N     P=0.511    |
|INCIDENTAL TUMOR       |  P=0.145N     P=0.163N     P=0.046N*    P=0.110N   |  P=0.356      P=0.740      P=0.500N     P=0.511    |
|LOGISTIC REGRESSION    |  P=0.156N     P=0.163N     P=0.061N     P=0.130N   |  P=0.356      P=0.740      P=0.500N     P=0.511    |
|COCHRAN-ARMITAGE       |  P=0.078N                                          |  P=0.339                                           |
|FISHER EXACT           |               P=0.298N     P=0.074N     P=0.074N   |               P=0.742      P=0.505N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 19/50 (38%)  18/49 (37%)  16/50 (32%)  10/48 (21%) | 22/47 (47%)  18/50 (36%)  17/49 (35%)  14/49 (29%) |
|ADJUSTED (b)           |  55.2%        42.1%        42.7%        39.2%      |  56.7%        49.2%        43.1%        38.2%      |
|TERMINAL (d)           |  9/23 (39%)   9/33 (27%)   9/29 (31%)   9/24 (38%) | 15/31 (48%)  12/30 (40%)  11/32 (34%)  11/33 (33%) |
|FIRST INCIDENCE (DAYS) |   598          497          498          497       |   498          595          498          586       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.102N     P=0.212N     P=0.236N     P=0.063N   |  P=0.064N     P=0.335N     P=0.200N     P=0.060N   |
|INCIDENTAL TUMOR       |  P=0.096N     P=0.504      P=0.390N     P=0.121N   |  P=0.081N     P=0.191N     P=0.128N     P=0.048N*  |
|LOGISTIC REGRESSION    |  P=0.070N     P=0.514N     P=0.364N     P=0.121N   |  P=0.074N     P=0.237N     P=0.158N     P=0.059N   |
|COCHRAN-ARMITAGE       |  P=0.030N*                                         |  P=0.073N                                          |
|FISHER EXACT           |               P=0.531N     P=0.338N     P=0.050N*  |               P=0.191N     P=0.159N     P=0.051N   |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  10
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma, Basosquamous Tumor Benign, or Trichoepithelioma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         6.1%         0.0%         0.0%      |   0.0%         0.0%         3.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    2/33 (6%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.391N     P=0.321        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|INCIDENTAL TUMOR       |  P=0.391N     P=0.321        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|LOGISTIC REGRESSION    |  P=0.391N     P=0.321        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|COCHRAN-ARMITAGE       |  P=0.369N                                          |  P=0.786N                                          |
|FISHER EXACT           |               P=0.247        (e)          (e)      |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous Tumor (benign,                                                       |
|     malignant or NOS), or Trichoepithelioma                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         6.1%         0.0%         0.0%      |   0.0%         0.0%         3.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    2/33 (6%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.391N     P=0.321        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|INCIDENTAL TUMOR       |  P=0.391N     P=0.321        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|LOGISTIC REGRESSION    |  P=0.391N     P=0.321        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|COCHRAN-ARMITAGE       |  P=0.369N                                          |  P=0.786N                                          |
|FISHER EXACT           |               P=0.247        (e)          (e)      |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  11
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal                                                       |
|     Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepithelioma                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    3/50 (6%)    1/50 (2%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)  |
|ADJUSTED (b)           |   7.8%         9.1%         3.4%         0.0%      |   0.0%         0.0%         6.1%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    3/33 (9%)    1/29 (3%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    2/33 (6%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   700          729 (T)      729 (T)      ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.119N     P=0.654      P=0.438N     P=0.243N   |  P=0.685N       (e)        P=0.245        (e)      |
|INCIDENTAL TUMOR       |  P=0.138N     P=0.571      P=0.543N     P=0.347N   |  P=0.685N       (e)        P=0.245        (e)      |
|LOGISTIC REGRESSION    |  P=0.134N     P=0.598      P=0.491N     P=0.275N   |  P=0.685N       (e)        P=0.245        (e)      |
|COCHRAN-ARMITAGE       |  P=0.104N                                          |  P=0.697N                                          |
|FISHER EXACT           |               P=0.500      P=0.500N     P=0.247N   |                 (e)        P=0.247        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/50 (12%)   1/50 (2%)    6/50 (12%)   5/50 (10%) |  2/50 (4%)    1/50 (2%)    0/50 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |  19.5%         3.0%        17.7%        18.1%      |   5.5%         2.4%         0.0%         2.6%      |
|TERMINAL (d)           |  1/23 (4%)    1/33 (3%)    3/29 (10%)   3/24 (13%) |  1/32 (3%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   614          729 (T)      558          595       |   667          600          ---          671       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.293      P=0.033N*    P=0.550N     P=0.565N   |  P=0.484N     P=0.520N     P=0.242N     P=0.496N   |
|INCIDENTAL TUMOR       |  P=0.173      P=0.119N     P=0.355      P=0.440    |  P=0.510N     P=0.416N     P=0.236N     P=0.528N   |
|LOGISTIC REGRESSION    |  P=0.312      P=0.052N     P=0.605      P=0.615N   |  P=0.499N     P=0.497N     P=0.234N     P=0.503N   |
|COCHRAN-ARMITAGE       |  P=0.420                                           |  P=0.500N                                          |
|FISHER EXACT           |               P=0.056N     P=0.620N     P=0.500N   |               P=0.500N     P=0.247N     P=0.500N   |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  12
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/50 (12%)   3/50 (6%)    6/50 (12%)   5/50 (10%) |  2/50 (4%)    1/50 (2%)    1/50 (2%)    1/50 (2%)  |
|ADJUSTED (b)           |  19.5%         8.4%        17.7%        18.1%      |   5.5%         2.4%         3.0%         2.6%      |
|TERMINAL (d)           |  1/23 (4%)    2/33 (6%)    3/29 (10%)   3/24 (13%) |  1/32 (3%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   614          644          558          595       |   667          600          729 (T)      671       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.406      P=0.150N     P=0.550N     P=0.565N   |  P=0.471N     P=0.520N     P=0.499N     P=0.496N   |
|INCIDENTAL TUMOR       |  P=0.277      P=0.379N     P=0.355      P=0.440    |  P=0.493N     P=0.416N     P=0.493N     P=0.528N   |
|LOGISTIC REGRESSION    |  P=0.264      P=0.228N     P=0.605      P=0.615N   |  P=0.489N     P=0.497N     P=0.492N     P=0.503N   |
|COCHRAN-ARMITAGE       |  P=0.548                                           |  P=0.488N                                          |
|FISHER EXACT           |               P=0.243N     P=0.620N     P=0.500N   |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         5.5%         0.0%         0.0%      |   0.0%         0.0%         3.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    1/33 (3%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          644          ---          ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.408N     P=0.295        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|INCIDENTAL TUMOR       |  P=0.402N     P=0.237        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|LOGISTIC REGRESSION    |  P=0.397N     P=0.240        (e)          (e)      |  P=0.777N       (e)        P=0.506        (e)      |
|COCHRAN-ARMITAGE       |  P=0.369N                                          |  P=0.786N                                          |
|FISHER EXACT           |               P=0.247        (e)          (e)      |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  13
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    1/50 (2%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   7.8%         3.0%         0.0%         0.0%      |   0.0%         0.0%         3.0%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    1/33 (3%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   700          729 (T)      ---          ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.186N     P=0.385N     P=0.207N     P=0.243N   |  P=0.777N       (e)        P=0.506        (e)      |
|INCIDENTAL TUMOR       |  P=0.222N     P=0.494N     P=0.301N     P=0.347N   |  P=0.777N       (e)        P=0.506        (e)      |
|LOGISTIC REGRESSION    |  P=0.199N     P=0.439N     P=0.235N     P=0.275N   |  P=0.777N       (e)        P=0.506        (e)      |
|COCHRAN-ARMITAGE       |  P=0.169N                                          |  P=0.786N                                          |
|FISHER EXACT           |               P=0.500N     P=0.247N     P=0.247N   |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Melanoma Malignant                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         6.1%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    2/33 (6%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.391N     P=0.321        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.391N     P=0.321        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.391N     P=0.321        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.369N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.247        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  14
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    1/50 (2%)    1/50 (2%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   7.8%         3.0%         3.4%         0.0%      |   0.0%         0.0%         3.0%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    1/33 (3%)    1/29 (3%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   700          729 (T)      729 (T)      ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.216N     P=0.385N     P=0.438N     P=0.243N   |  P=0.777N       (e)        P=0.506        (e)      |
|INCIDENTAL TUMOR       |  P=0.252N     P=0.494N     P=0.543N     P=0.347N   |  P=0.777N       (e)        P=0.506        (e)      |
|LOGISTIC REGRESSION    |  P=0.235N     P=0.439N     P=0.491N     P=0.275N   |  P=0.777N       (e)        P=0.506        (e)      |
|COCHRAN-ARMITAGE       |  P=0.194N                                          |  P=0.786N                                          |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.247N   |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    1/50 (2%)    1/50 (2%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   7.8%         3.0%         3.4%         0.0%      |   0.0%         0.0%         3.0%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    1/33 (3%)    1/29 (3%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   700          729 (T)      729 (T)      ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.216N     P=0.385N     P=0.438N     P=0.243N   |  P=0.777N       (e)        P=0.506        (e)      |
|INCIDENTAL TUMOR       |  P=0.252N     P=0.494N     P=0.543N     P=0.347N   |  P=0.777N       (e)        P=0.506        (e)      |
|LOGISTIC REGRESSION    |  P=0.235N     P=0.439N     P=0.491N     P=0.275N   |  P=0.777N       (e)        P=0.506        (e)      |
|COCHRAN-ARMITAGE       |  P=0.194N                                          |  P=0.786N                                          |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.247N   |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  15
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/49 (0%)    2/50 (4%)    1/50 (2%)    0/49 (0%)  |  0/50 (0%)    0/48 (0%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         6.1%         3.4%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    2/33 (6%)    1/29 (3%)    0/24 (0%)  |  0/32 (0%)    0/29 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      729 (T)      ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.406N     P=0.321      P=0.546        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.406N     P=0.321      P=0.546        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.406N     P=0.321      P=0.546        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.380N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.253      P=0.505        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 46/50 (92%)  42/50 (84%)  42/50 (84%)  44/50 (88%) |                                                    |
|ADJUSTED (b)           | 100.0%        97.6%        97.6%        97.8%      |                                                    |
|TERMINAL (d)           | 23/23 (100%) 32/33 (97%)  28/29 (97%)  23/24 (96%) |                                                    |
|FIRST INCIDENCE (DAYS) |   529          372          425          387       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.101      P=0.006N**   P=0.087N     P=0.478    |                                                    |
|INCIDENTAL TUMOR       |  P=0.146      P=0.069N     P=0.192N     P=0.486    |                                                    |
|LOGISTIC REGRESSION    |  P=0.046 *    P=0.174N     P=0.348N     P=0.271    |                                                    |
|COCHRAN-ARMITAGE       |  P=0.539N                                          |                                                    |
|FISHER EXACT           |               P=0.178N     P=0.178N     P=0.370N   |                                                    |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  16
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Thymus                                                                                                                           |
|     Thymoma: Benign, Malignant, NOS                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/49 (0%)    0/47 (0%)    2/47 (4%)    0/50 (0%)  |  0/49 (0%)    0/49 (0%)    0/48 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         6.5%         0.0%      |   0.0%         0.0%         0.0%         2.4%      |
|TERMINAL (d)           |  0/22 (0%)    0/32 (0%)    1/27 (4%)    0/24 (0%)  |  0/32 (0%)    0/29 (0%)    0/32 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          639          ---       |   ---          ---          ---          642       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.735N       (e)        P=0.259        (e)      |  P=0.222        (e)          (e)        P=0.505    |
|INCIDENTAL TUMOR       |  P=0.727N       (e)        P=0.236        (e)      |  P=0.226        (e)          (e)        P=0.682    |
|LOGISTIC REGRESSION    |  P=0.722N       (e)        P=0.223        (e)      |  P=0.221        (e)          (e)        P=0.515    |
|COCHRAN-ARMITAGE       |  P=0.687N                                          |  P=0.218                                           |
|FISHER EXACT           |                 (e)        P=0.237        (e)      |                 (e)          (e)        P=0.505    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/50 (10%)   1/50 (2%)    3/50 (6%)    1/50 (2%)  |  3/50 (6%)    8/50 (16%)   5/50 (10%)   6/50 (12%) |
|ADJUSTED (b)           |  15.4%         3.0%         8.1%         3.3%      |   8.9%        26.7%        15.2%        17.3%      |
|TERMINAL (d)           |  2/23 (9%)    1/33 (3%)    1/29 (3%)    0/24 (0%)  |  2/32 (6%)    8/30 (27%)   5/33 (15%)   5/33 (15%) |
|FIRST INCIDENCE (DAYS) |   546          729 (T)      526          642       |   678          729 (T)      729 (T)      648       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.243N     P=0.068N     P=0.344N     P=0.147N   |  P=0.486      P=0.079      P=0.369      P=0.258    |
|INCIDENTAL TUMOR       |  P=0.150N     P=0.120N     P=0.355N     P=0.130N   |  P=0.477      P=0.077      P=0.371      P=0.240    |
|LOGISTIC REGRESSION    |  P=0.150N     P=0.104N     P=0.322N     P=0.107N   |  P=0.474      P=0.073      P=0.368      P=0.243    |
|COCHRAN-ARMITAGE       |  P=0.169N                                          |  P=0.442                                           |
|FISHER EXACT           |               P=0.102N     P=0.357N     P=0.102N   |               P=0.100      P=0.357      P=0.243    |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  17
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    2/50 (4%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |
|ADJUSTED (b)           |   4.3%         5.7%         0.0%         0.0%      |   0.0%         0.0%         2.9%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    1/33 (3%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      706          ---          ---       |   ---          ---          723          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.229N     P=0.619      P=0.454N     P=0.492N   |  P=0.778N       (e)        P=0.512        (e)      |
|INCIDENTAL TUMOR       |  P=0.273N     P=0.506      P=0.454N     P=0.492N   |  P=0.800N       (e)        P=0.500        (e)      |
|LOGISTIC REGRESSION    |  P=0.245N     P=0.568      P=0.454N     P=0.492N   |  P=0.781N       (e)        P=0.505        (e)      |
|COCHRAN-ARMITAGE       |  P=0.209N                                          |  P=0.786N                                          |
|FISHER EXACT           |               P=0.500      P=0.500N     P=0.500N   |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/50 (12%)   3/50 (6%)    3/50 (6%)    1/50 (2%)  |  3/50 (6%)    8/50 (16%)   6/50 (12%)   6/50 (12%) |
|ADJUSTED (b)           |  19.5%         8.6%         8.1%         3.3%      |   8.9%        26.7%        17.6%        17.3%      |
|TERMINAL (d)           |  3/23 (13%)   2/33 (6%)    1/29 (3%)    0/24 (0%)  |  2/32 (6%)    8/30 (27%)   5/33 (15%)   5/33 (15%) |
|FIRST INCIDENCE (DAYS) |   546          706          526          642       |   678          729 (T)      723          648       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.110N     P=0.142N     P=0.224N     P=0.086N   |  P=0.494      P=0.079      P=0.258      P=0.258    |
|INCIDENTAL TUMOR       |  P=0.072N     P=0.263N     P=0.229N     P=0.074N   |  P=0.480      P=0.077      P=0.254      P=0.240    |
|LOGISTIC REGRESSION    |  P=0.071N     P=0.237N     P=0.224N     P=0.069N   |  P=0.482      P=0.073      P=0.251      P=0.243    |
|COCHRAN-ARMITAGE       |  P=0.068N                                          |  P=0.449                                           |
|FISHER EXACT           |               P=0.243N     P=0.243N     P=0.056N   |               P=0.100      P=0.243      P=0.243    |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  18
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    2/50 (4%)    1/50 (2%)  |  1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         6.9%         4.2%      |   3.1%         0.0%         0.0%         3.0%      |
|TERMINAL (d)           |  0/23 (0%)    0/33 (0%)    2/29 (7%)    1/24 (4%)  |  1/32 (3%)    0/30 (0%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      729 (T)   |   729 (T)      ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.310        (e)        P=0.290      P=0.508    |  P=0.549      P=0.513N     P=0.494N     P=0.755N   |
|INCIDENTAL TUMOR       |  P=0.310        (e)        P=0.290      P=0.508    |  P=0.549      P=0.513N     P=0.494N     P=0.755N   |
|LOGISTIC REGRESSION    |  P=0.310        (e)        P=0.290      P=0.508    |  P=0.549      P=0.513N     P=0.494N     P=0.755N   |
|COCHRAN-ARMITAGE       |  P=0.350                                           |  P=0.536                                           |
|FISHER EXACT           |                 (e)        P=0.247      P=0.500    |               P=0.500N     P=0.500N     P=0.753N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    2/50 (4%)    2/50 (4%)  |  1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         6.9%         8.3%      |   3.1%         0.0%         0.0%         3.0%      |
|TERMINAL (d)           |  0/23 (0%)    0/33 (0%)    2/29 (7%)    2/24 (8%)  |  1/32 (3%)    0/30 (0%)    0/33 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      729 (T)   |   729 (T)      ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.091        (e)        P=0.290      P=0.247    |  P=0.549      P=0.513N     P=0.494N     P=0.755N   |
|INCIDENTAL TUMOR       |  P=0.091        (e)        P=0.290      P=0.247    |  P=0.549      P=0.513N     P=0.494N     P=0.755N   |
|LOGISTIC REGRESSION    |  P=0.091        (e)        P=0.290      P=0.247    |  P=0.549      P=0.513N     P=0.494N     P=0.755N   |
|COCHRAN-ARMITAGE       |  P=0.122                                           |  P=0.536                                           |
|FISHER EXACT           |                 (e)        P=0.247      P=0.247    |               P=0.500N     P=0.500N     P=0.753N   |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  19
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  9/50 (18%)   7/50 (14%)  12/50 (24%)   7/50 (14%) |
|ADJUSTED (b)           |                                                    |  25.2%        17.5%        32.2%        18.3%      |
|TERMINAL (d)           |                                                    |  6/32 (19%)   2/30 (7%)    9/33 (27%)   4/33 (12%) |
|FIRST INCIDENCE (DAYS) |                                                    |   667          404          497          614       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.370N     P=0.449N     P=0.340      P=0.379N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.481N     P=0.493N     P=0.303      P=0.352N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.405N     P=0.388N     P=0.328      P=0.398N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.404N                                          |
|FISHER EXACT           |                                                    |               P=0.393N     P=0.312      P=0.393N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/50 (2%)    1/50 (2%)    3/50 (6%)    0/50 (0%)  |
|ADJUSTED (b)           |                                                    |   2.2%         2.2%         7.5%         0.0%      |
|TERMINAL (d)           |                                                    |  0/32 (0%)    0/30 (0%)    1/33 (3%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   533          579          541          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.333N     P=0.753N     P=0.319      P=0.500N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.449N     P=0.770N     P=0.249      P=0.748N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.328N     P=0.715N     P=0.239      P=0.423N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.339N                                          |
|FISHER EXACT           |                                                    |               P=0.753N     P=0.309      P=0.500N   |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  20
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   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)            |                                                    | 10/50 (20%)   8/50 (16%)  14/50 (28%)   7/50 (14%) |
|ADJUSTED (b)           |                                                    |  26.9%        19.3%        35.3%        18.3%      |
|TERMINAL (d)           |                                                    |  6/32 (19%)   2/30 (7%)    9/33 (27%)   4/33 (12%) |
|FIRST INCIDENCE (DAYS) |                                                    |   533          404          497          614       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.274N     P=0.449N     P=0.277      P=0.291N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.407N     P=0.487N     P=0.210      P=0.312N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.293N     P=0.374N     P=0.241      P=0.304N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.295N                                          |
|FISHER EXACT           |                                                    |               P=0.398N     P=0.241      P=0.298N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         5.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    0/33 (0%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          558          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.716        (e)        P=0.226        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.728        (e)        P=0.210        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.621N       (e)        P=0.280        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.697N                                          |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.247        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  21
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)  |  1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         5.0%         0.0%      |   3.1%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    0/33 (0%)    0/29 (0%)    0/24 (0%)  |  1/32 (3%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          558          ---       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.716        (e)        P=0.226        (e)      |  P=0.466N     P=0.513N     P=0.494N     P=0.494N   |
|INCIDENTAL TUMOR       |  P=0.728        (e)        P=0.210        (e)      |  P=0.466N     P=0.513N     P=0.494N     P=0.494N   |
|LOGISTIC REGRESSION    |  P=0.621N       (e)        P=0.280        (e)      |  P=0.466N     P=0.513N     P=0.494N     P=0.494N   |
|COCHRAN-ARMITAGE       |  P=0.697N                                          |  P=0.474N                                          |
|FISHER EXACT           |                 (e)        P=0.247        (e)      |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   7.9%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/23 (4%)    0/33 (0%)    0/29 (0%)    0/24 (0%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   719          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.264N     P=0.175N     P=0.207N     P=0.248N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.319N     P=0.268N     P=0.301N     P=0.347N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.272N     P=0.188N     P=0.224N     P=0.262N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.242N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.247N     P=0.247N     P=0.247N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  22
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 15/50 (30%)   5/50 (10%)   6/50 (12%)   6/50 (12%) | 10/50 (20%)   8/50 (16%)   9/50 (18%)  12/50 (24%) |
|ADJUSTED (b)           |  37.5%        14.0%        16.0%        21.8%      |  24.2%        22.0%        23.6%        30.0%      |
|TERMINAL (d)           |  3/23 (13%)   3/33 (9%)    0/29 (0%)    3/24 (13%) |  3/32 (9%)    3/30 (10%)   5/33 (15%)   6/33 (18%) |
|FIRST INCIDENCE (DAYS) |   529          706          572          643       |   441          478          541          421       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.223N     P=0.007N**   P=0.040N*    P=0.072N   |  P=0.303      P=0.450N     P=0.482N     P=0.430    |
|INCIDENTAL TUMOR       |  P=0.247N     P=0.049N*    P=0.090N     P=0.094N   |  P=0.131      P=0.578      P=0.557N     P=0.217    |
|LOGISTIC REGRESSION    |  P=0.356N     P=0.013N*    P=0.078N     P=0.199N   |  P=0.248      P=0.379N     P=0.527N     P=0.417    |
|COCHRAN-ARMITAGE       |  P=0.096N                                          |  P=0.247                                           |
|FISHER EXACT           |               P=0.011N*    P=0.024N*    P=0.024N*  |               P=0.398N     P=0.500N     P=0.405    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma: Benign, Malignant, NOS                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    2/50 (4%)    4/50 (8%)    3/50 (6%)  |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |   2.2%         5.1%        11.2%        11.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/23 (0%)    0/33 (0%)    2/29 (7%)    2/24 (8%)  |  0/32 (0%)    0/30 (0%)    0/33 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   572          624          498          552       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.209      P=0.536      P=0.194      P=0.266    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.255      P=0.338      P=0.208      P=0.250    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.328      P=0.508      P=0.210      P=0.294    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.304                                           |    (e)                                             |
|FISHER EXACT           |               P=0.500      P=0.181      P=0.309    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  23
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |
|                       |   CONTROL      MG/KG                               |   CONTROL      MG/KG                               |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 49/50 (98%)  49/50 (98%)  48/50 (96%)  46/50 (92%) | 37/50 (74%)  39/50 (78%)  32/50 (64%)  30/50 (60%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  84.0%        88.5%        75.6%        69.4%      |
|TERMINAL (d)           | 23/23 (100%) 33/33 (100%) 29/29 (100%) 24/24 (100%)| 25/32 (78%)  25/30 (83%)  23/33 (70%)  20/33 (61%) |
|FIRST INCIDENCE (DAYS) |   529          372          425          387       |   498          404          497          393       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.193      P=0.042N*    P=0.217N     P=0.510    |  P=0.044N*    P=0.297      P=0.199N     P=0.128N   |
|INCIDENTAL TUMOR       |  P=0.509      P=0.602      P=0.730      P=0.556    |  P=0.047N*    P=0.348      P=0.164N     P=0.098N   |
|LOGISTIC REGRESSION    |  P=0.544      P=0.420      P=0.730      P=0.647    |  P=0.036N*    P=0.309      P=0.153N     P=0.112N   |
|COCHRAN-ARMITAGE       |  P=0.073N                                          |  P=0.037N*                                         |
|FISHER EXACT           |               P=0.753N     P=0.500N     P=0.181N   |               P=0.408      P=0.194N     P=0.101N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 23/50 (46%)  18/50 (36%)  14/50 (28%)  14/50 (28%) | 18/50 (36%)  11/50 (22%)  16/50 (32%)  14/50 (28%) |
|ADJUSTED (b)           |  55.4%        42.7%        34.9%        43.3%      |  40.2%        27.9%        37.0%        35.2%      |
|TERMINAL (d)           |  6/23 (26%)  10/33 (30%)   4/29 (14%)   7/24 (29%) |  7/32 (22%)   3/30 (10%)   7/33 (21%)   8/33 (24%) |
|FIRST INCIDENCE (DAYS) |   529          372          498          306       |   399          478          497          421       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.263N     P=0.083N     P=0.067N     P=0.151N   |  P=0.400N     P=0.154N     P=0.399N     P=0.274N   |
|INCIDENTAL TUMOR       |  P=0.176N     P=0.483N     P=0.199N     P=0.181N   |  P=0.441      P=0.183N     P=0.500N     P=0.534N   |
|LOGISTIC REGRESSION    |  P=0.120N     P=0.217N     P=0.128N     P=0.071N   |  P=0.512      P=0.071N     P=0.482N     P=0.392N   |
|COCHRAN-ARMITAGE       |  P=0.067N                                          |  P=0.441N                                          |
|FISHER EXACT           |               P=0.208N     P=0.048N*    P=0.048N*  |               P=0.093N     P=0.417N     P=0.260N   |
|=================================================================================================================================|
         DATE: 07/11/96                     EXPERIMENT: 05067 TEST: 09                                                 PAGE  24
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- THEOPHYLLINE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      7.5          25 MG/KG     75 MG/KG  |   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)            | 49/50 (98%)  49/50 (98%)  48/50 (96%)  47/50 (94%) | 44/50 (88%)  41/50 (82%)  40/50 (80%)  36/50 (72%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  88.0%        89.1%        84.9%        78.1%      |
|TERMINAL (d)           | 23/23 (100%) 33/33 (100%) 29/29 (100%) 24/24 (100%)| 26/32 (81%)  25/30 (83%)  26/33 (79%)  23/33 (70%) |
|FIRST INCIDENCE (DAYS) |   529          372          425          306       |   399          404          497          393       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.147      P=0.042N*    P=0.217N     P=0.452    |  P=0.077N     P=0.519N     P=0.265N     P=0.117N   |
|INCIDENTAL TUMOR       |  P=0.358      P=0.602      P=0.730      P=0.556    |  P=0.105N     P=0.464N     P=0.221N     P=0.147N   |
|LOGISTIC REGRESSION    |  P=0.263      P=0.420      P=0.730      P=0.325    |  P=0.100N     P=0.339N     P=0.219N     P=0.130N   |
|COCHRAN-ARMITAGE       |  P=0.181N                                          |  P=0.036N*                                         |
|FISHER EXACT           |               P=0.753N     P=0.500N     P=0.309N   |               P=0.288N     P=0.207N     P=0.039N*  |
|=================================================================================================================================|
 (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).