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TDMS Study 05092-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                  O-NITROANISOLE                                    DATE: 09/12/94       
EXPERIMENT: 05092 TEST: 01                                                                                     TIME: 16:30:04       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-45038          ROUTE: DOSED FEED                                                                  NTP C#: C60388       
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 0091-23-6       
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Southern Research Inst                                  O-NITROANISOLE                                    DATE: 09/12/94      
EXPERIMENT: 05092 TEST: 01                                                                                     TIME: 16:30:04      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-45038          ROUTE: DOSED FEED                                                                  NTP C#: C60388      
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 0091-23-6      
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    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                                  O-NITROANISOLE                                    DATE: 09/12/94       
EXPERIMENT: 05092 TEST: 01                                                                                     TIME: 16:30:04       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-45038          ROUTE: DOSED FEED                                                                  NTP C#: C60388       
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 0091-23-6       
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                         IN THE ANALYSIS OF THE STUDY OF O-NITROANISOLE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma Malignant
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Clitoral/Preputial Gland      Carcinoma
                                                           Carcinoma or Adenoma
                             Kidney: Renal Tubule          Carcinoma
                                                           Carcinoma or Adenoma
                             Lung                          Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Pancreas                      Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Stomach, Forestomach          Squamous Cell Carcinoma or Papilloma Squamous
                             Testes                        Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                  O-NITROANISOLE                                    DATE: 09/12/94       
EXPERIMENT: 05092 TEST: 01                                                                                     TIME: 16:30:04       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-45038          ROUTE: DOSED FEED                                                                  NTP C#: C60388       
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 0091-23-6       
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                         IN THE ANALYSIS OF THE STUDY OF O-NITROANISOLE
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Mammary Gland                 Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pancreas                      Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Malignant Tumors
 
              ====================================================================================================
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   1
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/58 (3%)    0/60 (0%)    1/60 (2%)    0/59 (0%)  |  1/60 (2%)    5/60 (8%)    0/60 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   6.7%         0.0%         4.2%         0.0%      |   2.5%        12.2%         0.0%         6.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/30 (7%)    0/34 (0%)    1/24 (4%)    0/9 (0%)   |  0/33 (0%)    5/41 (12%)   0/26 (0%)    2/33 (6%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      ---          728 (T)      ---       |   687          728 (T)      ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.520N     P=0.211N     P=0.578N     P=0.526N   |  P=0.541N     P=0.156      P=0.557N     P=0.491    |
|INCIDENTAL TUMOR       |  P=0.520N     P=0.211N     P=0.578N     P=0.526N   |  P=0.543N     P=0.118      P=0.545N     P=0.459    |
|LOGISTIC REGRESSION    |  P=0.520N     P=0.211N     P=0.578N     P=0.526N   |  P=0.539N     P=0.129      P=0.519N     P=0.489    |
|COCHRAN-ARMITAGE       |  P=0.265N                                          |  P=0.500N                                          |
|FISHER EXACT           |               P=0.239N     P=0.487N     P=0.244N   |               P=0.103      P=0.500N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/59 (12%)   7/60 (12%)   8/60 (13%)  10/59 (17%) |  1/60 (2%)    0/60 (0%)    0/60 (0%)    1/59 (2%)  |
|ADJUSTED (b)           |  18.9%        20.6%        25.8%        73.0%      |   3.0%         0.0%         0.0%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  3/31 (10%)   7/34 (21%)   3/24 (13%)   6/9 (67%)  |  1/33 (3%)    0/41 (0%)    0/26 (0%)    1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   669          728 (T)      604          613       |   728 (T)      ---          ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.563N     P=0.352      P=0.003 ** |  P=0.513      P=0.457N     P=0.548N     P=0.755    |
|INCIDENTAL TUMOR       |  P=0.054      P=0.587      P=0.571N     P=0.090    |  P=0.513      P=0.457N     P=0.548N     P=0.755    |
|LOGISTIC REGRESSION    |  P=0.017 *    P=0.597N     P=0.473      P=0.042 *  |  P=0.513      P=0.457N     P=0.548N     P=0.755    |
|COCHRAN-ARMITAGE       |  P=0.217                                           |  P=0.537                                           |
|FISHER EXACT           |               P=0.598N     P=0.514      P=0.301    |               P=0.500N     P=0.500N     P=0.748    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   2
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/59 (10%)   3/60 (5%)    2/60 (3%)    0/59 (0%)  |  0/60 (0%)    0/60 (0%)    1/60 (2%)    1/59 (2%)  |
|ADJUSTED (b)           |  18.2%         8.4%         7.7%         0.0%      |   0.0%         0.0%         2.6%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  5/31 (16%)   2/34 (6%)    1/24 (4%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   669          682          718          ---       |   ---          ---          613          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.119N     P=0.213N     P=0.224N     P=0.173N   |  P=0.289        (e)        P=0.467      P=0.494    |
|INCIDENTAL TUMOR       |  P=0.044N*    P=0.245N     P=0.151N     P=0.107N   |  P=0.364        (e)        P=0.739      P=0.494    |
|LOGISTIC REGRESSION    |  P=0.058N     P=0.227N     P=0.165N     P=0.094N   |  P=0.298        (e)        P=0.511      P=0.494    |
|COCHRAN-ARMITAGE       |  P=0.018N*                                         |  P=0.302                                           |
|FISHER EXACT           |               P=0.237N     P=0.131N     P=0.014N*  |                 (e)        P=0.500      P=0.496    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 12/59 (20%)  10/60 (17%)  10/60 (17%)  10/59 (17%) |  1/60 (2%)    0/60 (0%)    1/60 (2%)    2/59 (3%)  |
|ADJUSTED (b)           |  32.2%        28.5%        31.9%        73.0%      |   3.0%         0.0%         2.6%         6.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  7/31 (23%)   9/34 (26%)   4/24 (17%)   6/9 (67%)  |  1/33 (3%)    0/41 (0%)    0/26 (0%)    2/32 (6%)  |
|FIRST INCIDENCE (DAYS) |   669          682          604          613       |   728 (T)      ---          613          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.007 **   P=0.346N     P=0.568      P=0.030 *  |  P=0.211      P=0.457N     P=0.715      P=0.489    |
|INCIDENTAL TUMOR       |  P=0.308      P=0.433N     P=0.285N     P=0.350    |  P=0.256      P=0.457N     P=0.672N     P=0.489    |
|LOGISTIC REGRESSION    |  P=0.157      P=0.379N     P=0.449N     P=0.252    |  P=0.217      P=0.457N     P=0.751      P=0.489    |
|COCHRAN-ARMITAGE       |  P=0.441N                                          |  P=0.230                                           |
|FISHER EXACT           |               P=0.390N     P=0.390N     P=0.407N   |               P=0.500N     P=0.752N     P=0.494    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   3
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Chondroma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         5.1%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    1/34 (3%)    0/24 (0%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          638          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.540N     P=0.252        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.342N     P=0.246        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.427N     P=0.235        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.380N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/60 (0%)    0/60 (0%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   4.8%         0.0%         0.0%         2.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    0/24 (0%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      ---          ---          481       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.673      P=0.237N     P=0.261N     P=0.617N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.456N     P=0.279N     P=0.183N     P=0.319N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.584N     P=0.210N     P=0.228N     P=0.395N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.646N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.500N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   4
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    0/60 (0%)    1/60 (2%)    1/59 (2%)  |  3/55 (5%)    5/57 (9%)    4/60 (7%)    3/58 (5%)  |
|ADJUSTED (b)           |  11.3%         0.0%         4.2%         5.6%      |  10.0%        13.2%        11.6%         9.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |  3/32 (9%)    0/34 (0%)    1/24 (4%)    0/9 (0%)   |  3/30 (10%)   5/38 (13%)   1/26 (4%)    3/31 (10%) |
|FIRST INCIDENCE (DAYS) |   603          ---          728 (T)      686       |   728 (T)      728 (T)      456 (I)      728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.620N     P=0.060N     P=0.257N     P=0.523N   |  P=0.492N     P=0.491      P=0.421      P=0.650N   |
|INCIDENTAL TUMOR       |  P=0.413N     P=0.059N     P=0.244N     P=0.296N   |  P=0.482N     P=0.491      P=0.456      P=0.650N   |
|LOGISTIC REGRESSION    |  P=0.442N     P=0.065N     P=0.199N     P=0.332N   |  P=0.454N     P=0.491      P=0.515      P=0.650N   |
|COCHRAN-ARMITAGE       |  P=0.303N                                          |  P=0.424N                                          |
|FISHER EXACT           |               P=0.059N     P=0.182N     P=0.187N   |               P=0.378      P=0.549      P=0.635N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/60 (12%)   5/60 (8%)    4/60 (7%)    9/59 (15%) |  4/55 (7%)    1/57 (2%)    3/60 (5%)    2/58 (3%)  |
|ADJUSTED (b)           |  19.4%        13.5%        10.5%        46.1%      |  11.9%         2.6%         9.4%         6.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   1/10 (10%)   1/9 (11%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  5/32 (16%)   4/34 (12%)   1/24 (4%)    3/9 (33%)  |  3/30 (10%)   1/38 (3%)    1/26 (4%)    1/31 (3%)  |
|FIRST INCIDENCE (DAYS) |   599          458 (I)      458 (I)      457 (I)   |   518          728 (T)      641          722       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.005 **   P=0.358N     P=0.383N     P=0.023 *  |  P=0.483N     P=0.128N     P=0.579N     P=0.329N   |
|INCIDENTAL TUMOR       |  P=0.096      P=0.370N     P=0.283N     P=0.194    |  P=0.404N     P=0.161N     P=0.443N     P=0.322N   |
|LOGISTIC REGRESSION    |  P=0.137      P=0.390N     P=0.272N     P=0.235    |  P=0.443N     P=0.159N     P=0.483N     P=0.319N   |
|COCHRAN-ARMITAGE       |  P=0.191                                           |  P=0.426N                                          |
|FISHER EXACT           |               P=0.381N     P=0.264N     P=0.381    |               P=0.171N     P=0.451N     P=0.314N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   5
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/60 (18%)   5/60 (8%)    5/60 (8%)   10/59 (17%) |  7/55 (13%)   6/57 (11%)   6/60 (10%)   5/58 (9%)  |
|ADJUSTED (b)           |  29.9%        13.5%        14.4%        49.1%      |  21.7%        15.8%        17.6%        15.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   1/10 (10%)   1/9 (11%)  |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |  8/32 (25%)   4/34 (12%)   2/24 (8%)    3/9 (33%)  |  6/30 (20%)   6/38 (16%)   2/26 (8%)    4/31 (13%) |
|FIRST INCIDENCE (DAYS) |   599          458 (I)      458 (I)      457 (I)   |   518          728 (T)      456 (I)      722       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.010 *    P=0.079N     P=0.185N     P=0.060    |  P=0.410N     P=0.333N     P=0.603N     P=0.360N   |
|INCIDENTAL TUMOR       |  P=0.179      P=0.081N     P=0.120N     P=0.410    |  P=0.356N     P=0.371N     P=0.491N     P=0.354N   |
|LOGISTIC REGRESSION    |  P=0.232      P=0.092N     P=0.098N     P=0.447    |  P=0.359N     P=0.406N     P=0.479N     P=0.354N   |
|COCHRAN-ARMITAGE       |  P=0.349                                           |  P=0.328N                                          |
|FISHER EXACT           |               P=0.089N     P=0.089N     P=0.517N   |               P=0.472N     P=0.433N     P=0.344N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/60 (0%)    0/60 (0%)    0/59 (0%)  |  0/55 (0%)    0/57 (0%)    0/60 (0%)    0/58 (0%)  |
|ADJUSTED (b)           |   5.5%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    0/24 (0%)    0/9 (0%)   |  0/30 (0%)    0/38 (0%)    0/26 (0%)    0/31 (0%)  |
|FIRST INCIDENCE (DAYS) |   676          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.350N     P=0.237N     P=0.274N     P=0.431N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.155N     P=0.316N     P=0.128N     P=0.139N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.272N     P=0.241N     P=0.245N     P=0.314N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.241N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.252N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   6
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    4/59 (7%)    4/60 (7%)    2/58 (3%)  |  2/60 (3%)    1/60 (2%)    2/59 (3%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.1%        11.8%        11.9%         5.9%      |   5.4%         2.2%         5.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    4/34 (12%)   1/24 (4%)    0/9 (0%)   |  1/33 (3%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      728 (T)      596          518       |   673          672          633          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.257      P=0.197      P=0.140      P=0.307    |  P=0.242N     P=0.456N     P=0.608      P=0.251N   |
|INCIDENTAL TUMOR       |  P=0.606N     P=0.197      P=0.230      P=0.564    |  P=0.190N     P=0.635N     P=0.671N     P=0.279N   |
|LOGISTIC REGRESSION    |  P=0.550      P=0.197      P=0.176      P=0.492    |  P=0.211N     P=0.489N     P=0.663      P=0.243N   |
|COCHRAN-ARMITAGE       |  P=0.554N                                          |  P=0.209N                                          |
|FISHER EXACT           |               P=0.182      P=0.187      P=0.494    |               P=0.500N     P=0.684      P=0.248N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    4/59 (7%)    4/60 (7%)    2/58 (3%)  |  2/60 (3%)    1/60 (2%)    3/59 (5%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.1%        11.8%        11.9%         5.9%      |   5.4%         2.2%         8.2%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    4/34 (12%)   1/24 (4%)    0/9 (0%)   |  1/33 (3%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      728 (T)      596          518       |   673          672          610          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.257      P=0.197      P=0.140      P=0.307    |  P=0.255N     P=0.456N     P=0.407      P=0.251N   |
|INCIDENTAL TUMOR       |  P=0.606N     P=0.197      P=0.230      P=0.564    |  P=0.166N     P=0.635N     P=0.626      P=0.279N   |
|LOGISTIC REGRESSION    |  P=0.550      P=0.197      P=0.176      P=0.492    |  P=0.153N     P=0.489N     P=0.472      P=0.243N   |
|COCHRAN-ARMITAGE       |  P=0.554N                                          |  P=0.221N                                          |
|FISHER EXACT           |               P=0.182      P=0.187      P=0.494    |               P=0.500N     P=0.492      P=0.248N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   7
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Mixed Tumor Benign                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    0/59 (0%)    2/60 (3%)    1/58 (2%)  |  0/60 (0%)    0/60 (0%)    0/59 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         5.4%        11.1%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    0/24 (0%)    1/9 (11%)  |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          667          728 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.138        (e)        P=0.211      P=0.249    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.393        (e)        P=0.385      P=0.249    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.269        (e)        P=0.239      P=0.249    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.349                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.252      P=0.496    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    0/60 (0%)    0/60 (0%)    2/59 (3%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%        17.9%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    0/24 (0%)    1/9 (11%)  |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          697       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002 **     (e)          (e)        P=0.051    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.021 *      (e)          (e)        P=0.153    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.007 **     (e)          (e)        P=0.088    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.041 *                                         |    (e)                                             |
|FISHER EXACT           |                 (e)          (e)        P=0.248    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   8
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    1/60 (2%)    1/60 (2%)    3/59 (5%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         2.9%         4.2%        21.9%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    1/34 (3%)    1/24 (4%)    1/9 (11%)  |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          728 (T)      728 (T)      663       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.001 **   P=0.512      P=0.443      P=0.016 *  |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.017 *    P=0.512      P=0.443      P=0.097    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.010 *    P=0.512      P=0.443      P=0.046 *  |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.063                                           |    (e)                                             |
|FISHER EXACT           |               P=0.504      P=0.504      P=0.122    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    3/60 (5%)    1/60 (2%)    2/60 (3%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    3/60 (5%)  |
|ADJUSTED (b)           |   0.0%         8.8%         4.2%        12.4%      |   0.0%         0.0%         0.0%         9.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    3/34 (9%)    1/24 (4%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    3/33 (9%)  |
|FIRST INCIDENCE (DAYS) |   ---          728 (T)      728 (T)      604       |   ---          ---          ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.096      P=0.131      P=0.443      P=0.106    |  P=0.008 **     (e)          (e)        P=0.120    |
|INCIDENTAL TUMOR       |  P=0.277      P=0.131      P=0.443      P=0.420    |  P=0.008 **     (e)          (e)        P=0.120    |
|LOGISTIC REGRESSION    |  P=0.238      P=0.131      P=0.443      P=0.196    |  P=0.008 **     (e)          (e)        P=0.120    |
|COCHRAN-ARMITAGE       |  P=0.430                                           |  P=0.009 **                                        |
|FISHER EXACT           |               P=0.122      P=0.500      P=0.248    |                 (e)          (e)        P=0.122    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE   9
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    4/60 (7%)    1/60 (2%)    2/60 (3%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    3/60 (5%)  |
|ADJUSTED (b)           |   0.0%        11.8%         4.2%        12.4%      |   0.0%         0.0%         0.0%         9.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    4/34 (12%)   1/24 (4%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    3/33 (9%)  |
|FIRST INCIDENCE (DAYS) |   ---          728 (T)      728 (T)      604       |   ---          ---          ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.137      P=0.070      P=0.443      P=0.106    |  P=0.008 **     (e)          (e)        P=0.120    |
|INCIDENTAL TUMOR       |  P=0.328      P=0.070      P=0.443      P=0.420    |  P=0.008 **     (e)          (e)        P=0.120    |
|LOGISTIC REGRESSION    |  P=0.303      P=0.070      P=0.443      P=0.196    |  P=0.008 **     (e)          (e)        P=0.120    |
|COCHRAN-ARMITAGE       |  P=0.533                                           |  P=0.009 **                                        |
|FISHER EXACT           |               P=0.059      P=0.500      P=0.248    |                 (e)          (e)        P=0.122    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    4/60 (7%)    1/60 (2%)    2/60 (3%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    3/60 (5%)  |
|ADJUSTED (b)           |   0.0%        11.8%         4.2%        12.4%      |   0.0%         0.0%         0.0%         9.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    4/34 (12%)   1/24 (4%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    3/33 (9%)  |
|FIRST INCIDENCE (DAYS) |   ---          728 (T)      728 (T)      604       |   ---          ---          ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.137      P=0.070      P=0.443      P=0.106    |  P=0.008 **     (e)          (e)        P=0.120    |
|INCIDENTAL TUMOR       |  P=0.328      P=0.070      P=0.443      P=0.420    |  P=0.008 **     (e)          (e)        P=0.120    |
|LOGISTIC REGRESSION    |  P=0.303      P=0.070      P=0.443      P=0.196    |  P=0.008 **     (e)          (e)        P=0.120    |
|COCHRAN-ARMITAGE       |  P=0.533                                           |  P=0.009 **                                        |
|FISHER EXACT           |               P=0.059      P=0.500      P=0.248    |                 (e)          (e)        P=0.122    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  10
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    3/60 (5%)    2/60 (3%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    3/60 (5%)    3/60 (5%)  |
|ADJUSTED (b)           |   6.9%         7.3%         8.3%         0.0%      |   0.0%         0.0%         9.4%         7.8%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   1/10 (10%)   0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    1/34 (3%)    2/24 (8%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    2/26 (8%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      457 (I)      728 (T)      ---       |   ---          ---          456 (I)      604       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.185N     P=0.648N     P=0.577N     P=0.200N   |  P=0.050 *      (e)        P=0.096      P=0.126    |
|INCIDENTAL TUMOR       |  P=0.096N     P=0.643      P=0.577N     P=0.104N   |  P=0.059        (e)        P=0.096      P=0.138    |
|LOGISTIC REGRESSION    |  P=0.067N     P=0.630N     P=0.493N     P=0.075N   |  P=0.054        (e)        P=0.121      P=0.118    |
|COCHRAN-ARMITAGE       |  P=0.075N                                          |  P=0.055                                           |
|FISHER EXACT           |               P=0.660N     P=0.500N     P=0.122N   |                 (e)        P=0.122      P=0.122    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    4/60 (7%)    3/60 (5%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    3/60 (5%)    3/60 (5%)  |
|ADJUSTED (b)           |   9.9%        10.1%        12.5%         0.0%      |   0.0%         0.0%         9.4%         7.8%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   1/10 (10%)   0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           |  2/32 (6%)    2/34 (6%)    3/24 (13%)   0/9 (0%)   |  0/33 (0%)    0/41 (0%)    2/26 (8%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      457 (I)      728 (T)      ---       |   ---          ---          456 (I)      604       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.163N     P=0.622N     P=0.610N     P=0.160N   |  P=0.050 *      (e)        P=0.096      P=0.126    |
|INCIDENTAL TUMOR       |  P=0.088N     P=0.633      P=0.610N     P=0.086N   |  P=0.059        (e)        P=0.096      P=0.138    |
|LOGISTIC REGRESSION    |  P=0.044N*    P=0.630N     P=0.502N     P=0.047N*  |  P=0.054        (e)        P=0.121      P=0.118    |
|COCHRAN-ARMITAGE       |  P=0.040N*                                         |  P=0.055                                           |
|FISHER EXACT           |               P=0.641N     P=0.500N     P=0.059N   |                 (e)        P=0.122      P=0.122    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  11
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  2/60 (3%)    0/60 (0%)    2/60 (3%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   6.1%         0.0%         5.2%         2.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    0/24 (0%)    0/9 (0%)   |  2/33 (6%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   728 (T)      ---          536          476       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.610N     P=0.192N     P=0.623      P=0.500N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.547N     P=0.192N     P=0.650      P=0.474N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.584N     P=0.192N     P=0.681      P=0.499N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.590N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.248N     P=0.691N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  3/60 (5%)    0/60 (0%)    2/60 (3%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         2.9%         0.0%         0.0%      |   9.1%         0.0%         5.2%         2.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    1/34 (3%)    0/24 (0%)    0/9 (0%)   |  3/33 (9%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          728 (T)      ---          ---       |   728 (T)      ---          536          476       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.800N     P=0.512        (e)          (e)      |  P=0.456N     P=0.086N     P=0.590N     P=0.306N   |
|INCIDENTAL TUMOR       |  P=0.800N     P=0.512        (e)          (e)      |  P=0.399N     P=0.086N     P=0.564N     P=0.287N   |
|LOGISTIC REGRESSION    |  P=0.800N     P=0.512        (e)          (e)      |  P=0.428N     P=0.086N     P=0.531N     P=0.308N   |
|COCHRAN-ARMITAGE       |  P=0.585N                                          |  P=0.430N                                          |
|FISHER EXACT           |               P=0.500        (e)          (e)      |               P=0.122N     P=0.500N     P=0.309N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  12
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    1/60 (2%)    2/60 (3%)    1/60 (2%)  | 17/60 (28%)  18/60 (30%)  15/60 (25%)   9/60 (15%) |
|ADJUSTED (b)           |   9.1%         2.9%         6.3%         7.7%      |  44.3%        40.5%        49.3%        25.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/32 (6%)    1/34 (3%)    1/24 (4%)    0/9 (0%)   | 13/33 (39%)  15/41 (37%)  12/26 (46%)   7/33 (21%) |
|FIRST INCIDENCE (DAYS) |   716          728 (T)      632          697       |   438          436          416          634       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.586      P=0.285N     P=0.590N     P=0.698    |  P=0.049N*    P=0.396N     P=0.480      P=0.064N   |
|INCIDENTAL TUMOR       |  P=0.410N     P=0.321N     P=0.517N     P=0.411N   |  P=0.024N*    P=0.545      P=0.590N     P=0.043N*  |
|LOGISTIC REGRESSION    |  P=0.548N     P=0.292N     P=0.534N     P=0.627N   |  P=0.034N*    P=0.561      P=0.522N     P=0.065N   |
|COCHRAN-ARMITAGE       |  P=0.340N                                          |  P=0.027N*                                         |
|FISHER EXACT           |               P=0.309N     P=0.500N     P=0.309N   |               P=0.500      P=0.418N     P=0.060N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    2/60 (3%)    2/60 (3%)    1/60 (2%)  | 17/60 (28%)  18/60 (30%)  15/60 (25%)   9/60 (15%) |
|ADJUSTED (b)           |   9.1%         5.9%         6.3%         7.7%      |  44.3%        40.5%        49.3%        25.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/32 (6%)    2/34 (6%)    1/24 (4%)    0/9 (0%)   | 13/33 (39%)  15/41 (37%)  12/26 (46%)   7/33 (21%) |
|FIRST INCIDENCE (DAYS) |   716          728 (T)      632          697       |   438          436          416          634       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.627      P=0.473N     P=0.590N     P=0.698    |  P=0.049N*    P=0.396N     P=0.480      P=0.064N   |
|INCIDENTAL TUMOR       |  P=0.374N     P=0.510N     P=0.517N     P=0.411N   |  P=0.024N*    P=0.545      P=0.590N     P=0.043N*  |
|LOGISTIC REGRESSION    |  P=0.488N     P=0.484N     P=0.534N     P=0.627N   |  P=0.034N*    P=0.561      P=0.522N     P=0.065N   |
|COCHRAN-ARMITAGE       |  P=0.268N                                          |  P=0.027N*                                         |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.309N   |               P=0.500      P=0.418N     P=0.060N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  13
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    2/60 (3%)    2/60 (3%)    1/60 (2%)  | 18/60 (30%)  18/60 (30%)  17/60 (28%)  10/60 (17%) |
|ADJUSTED (b)           |   9.1%         5.9%         6.3%         7.7%      |  47.1%        40.5%        51.9%        26.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/32 (6%)    2/34 (6%)    1/24 (4%)    0/9 (0%)   | 14/33 (42%)  15/41 (37%)  12/26 (46%)   7/33 (21%) |
|FIRST INCIDENCE (DAYS) |   716          728 (T)      632          697       |   438          436          416          476       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.627      P=0.473N     P=0.590N     P=0.698    |  P=0.067N     P=0.314N     P=0.379      P=0.071N   |
|INCIDENTAL TUMOR       |  P=0.374N     P=0.510N     P=0.517N     P=0.411N   |  P=0.029N*    P=0.531N     P=0.491      P=0.044N*  |
|LOGISTIC REGRESSION    |  P=0.488N     P=0.484N     P=0.534N     P=0.627N   |  P=0.044N*    P=0.518N     P=0.562      P=0.070N   |
|COCHRAN-ARMITAGE       |  P=0.268N                                          |  P=0.036N*                                         |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.309N   |               P=0.579N     P=0.500N     P=0.065N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/59 (8%)    3/59 (5%)    0/60 (0%)    5/58 (9%)  |  0/60 (0%)    0/60 (0%)    0/59 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |  15.6%         8.8%         0.0%        33.4%      |   0.0%         0.0%         0.0%         6.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  5/32 (16%)   3/34 (9%)    0/24 (0%)    1/9 (11%)  |  0/33 (0%)    0/41 (0%)    0/26 (0%)    2/33 (6%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      728 (T)      ---          613       |   ---          ---          ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.021 *    P=0.321N     P=0.062N     P=0.070    |  P=0.039 *      (e)          (e)        P=0.238    |
|INCIDENTAL TUMOR       |  P=0.158      P=0.321N     P=0.062N     P=0.353    |  P=0.039 *      (e)          (e)        P=0.238    |
|LOGISTIC REGRESSION    |  P=0.106      P=0.321N     P=0.062N     P=0.231    |  P=0.039 *      (e)          (e)        P=0.238    |
|COCHRAN-ARMITAGE       |  P=0.400                                           |  P=0.042 *                                         |
|FISHER EXACT           |               P=0.358N     P=0.027N*    P=0.618    |                 (e)          (e)        P=0.248    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  14
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 17/60 (28%)  12/60 (20%)   9/59 (15%)   4/59 (7%)  | 28/60 (47%)  30/60 (50%)  28/60 (47%)  20/60 (33%) |
|ADJUSTED (b)           |  41.5%        31.1%        30.0%        17.0%      |  66.3%        62.2%        67.0%        48.8%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   1/10 (10%)   0/10 (0%)    0/9 (0%)   |  0/10 (0%)    2/10 (20%)   1/10 (10%)   1/9 (11%)  |
|TERMINAL (d)           | 10/32 (31%)   9/34 (26%)   5/23 (22%)   0/9 (0%)   | 19/33 (58%)  23/41 (56%)  13/26 (50%)  13/33 (39%) |
|FIRST INCIDENCE (DAYS) |   457 (I)      456 (I)      557          518       |   613          456 (I)      457 (I)      386       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.186N     P=0.169N     P=0.192N     P=0.160N   |  P=0.119N     P=0.335N     P=0.216      P=0.124N   |
|INCIDENTAL TUMOR       |  P=0.008N**   P=0.195N     P=0.080N     P=0.007N** |  P=0.028N*    P=0.385      P=0.576      P=0.093N   |
|LOGISTIC REGRESSION    |  P=0.007N**   P=0.207N     P=0.074N     P=0.005N** |  P=0.036N*    P=0.526      P=0.574      P=0.102N   |
|COCHRAN-ARMITAGE       |  P=0.003N**                                        |  P=0.038N*                                         |
|FISHER EXACT           |               P=0.197N     P=0.066N     P=0.002N** |               P=0.428      P=0.573N     P=0.096N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 18/60 (30%)  12/60 (20%)  10/59 (17%)   4/59 (7%)  | 29/60 (48%)  30/60 (50%)  28/60 (47%)  20/60 (33%) |
|ADJUSTED (b)           |  44.2%        31.1%        32.5%        17.0%      |  68.7%        62.2%        67.0%        48.8%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   1/10 (10%)   0/10 (0%)    0/9 (0%)   |  0/10 (0%)    2/10 (20%)   1/10 (10%)   1/9 (11%)  |
|TERMINAL (d)           | 11/32 (34%)   9/34 (26%)   5/23 (22%)   0/9 (0%)   | 20/33 (61%)  23/41 (56%)  13/26 (50%)  13/33 (39%) |
|FIRST INCIDENCE (DAYS) |   457 (I)      456 (I)      557          518       |   613          456 (I)      457 (I)      386       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.177N     P=0.123N     P=0.214N     P=0.136N   |  P=0.100N     P=0.268N     P=0.260      P=0.092N   |
|INCIDENTAL TUMOR       |  P=0.006N**   P=0.142N     P=0.082N     P=0.006N** |  P=0.021N*    P=0.472      P=0.515N     P=0.064N   |
|LOGISTIC REGRESSION    |  P=0.005N**   P=0.154N     P=0.082N     P=0.003N** |  P=0.036N*    P=0.552N     P=0.522N     P=0.071N   |
|COCHRAN-ARMITAGE       |  P=0.002N**                                        |  P=0.030N*                                         |
|FISHER EXACT           |               P=0.146N     P=0.071N     P<0.001N** |               P=0.500      P=0.500N     P=0.068N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  15
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    1/60 (2%)    0/60 (0%)    2/60 (3%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   8.9%         2.9%         0.0%        10.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/32 (6%)    1/34 (3%)    0/24 (0%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   695          728 (T)      ---          632       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.324      P=0.290N     P=0.171N     P=0.478    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.649      P=0.321N     P=0.121N     P=0.525N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.511      P=0.301N     P=0.140N     P=0.675    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.617N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.309N     P=0.122N     P=0.500N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/60 (0%)    0/60 (0%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   5.2%         0.0%         0.0%        11.1%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    0/34 (0%)    0/24 (0%)    1/9 (11%)  |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   603          ---          ---          728 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.561      P=0.238N     P=0.274N     P=0.693    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.701      P=0.233N     P=0.253N     P=0.671N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.685      P=0.240N     P=0.240N     P=0.627N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.646N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.500N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  16
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/60 (10%)   2/60 (3%)    1/60 (2%)    3/60 (5%)  |  1/60 (2%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |  16.8%         5.9%         3.8%        20.0%      |   3.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  4/32 (13%)   2/34 (6%)    0/24 (0%)    1/9 (11%)  |  1/33 (3%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   603          728 (T)      722          632       |   728 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.347      P=0.125N     P=0.106N     P=0.515    |  P=0.486N     P=0.457N     P=0.548N     P=0.500N   |
|INCIDENTAL TUMOR       |  P=0.476N     P=0.136N     P=0.057N     P=0.395N   |  P=0.486N     P=0.457N     P=0.548N     P=0.500N   |
|LOGISTIC REGRESSION    |  P=0.614      P=0.136N     P=0.069N     P=0.495N   |  P=0.486N     P=0.457N     P=0.548N     P=0.500N   |
|COCHRAN-ARMITAGE       |  P=0.367N                                          |  P=0.472N                                          |
|FISHER EXACT           |               P=0.136N     P=0.057N     P=0.245N   |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    3/60 (5%)    2/60 (3%)    1/60 (2%)  |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.1%         8.0%         6.3%         7.1%      |   0.0%         4.9%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    2/34 (6%)    1/24 (4%)    0/9 (0%)   |  0/33 (0%)    2/41 (5%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      638          632          695       |   ---          728 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.519      P=0.327      P=0.436      P=0.503    |  P=0.400N     P=0.287        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.466N     P=0.323      P=0.451      P=0.708    |  P=0.400N     P=0.287        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.582N     P=0.302      P=0.482      P=0.608    |  P=0.400N     P=0.287        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.424N                                          |  P=0.380N                                          |
|FISHER EXACT           |               P=0.309      P=0.500      P=0.752N   |               P=0.248        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  17
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         4.3%         0.0%         0.0%      |   0.0%         2.4%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    0/24 (0%)    0/9 (0%)   |  0/33 (0%)    1/41 (2%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          456 (I)      ---          ---       |   ---          728 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.457N     P=0.246        (e)          (e)      |  P=0.598N     P=0.543        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.326N     P=0.201        (e)          (e)      |  P=0.598N     P=0.543        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.345N     P=0.261        (e)          (e)      |  P=0.598N     P=0.543        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.380N                                          |  P=0.585N                                          |
|FISHER EXACT           |               P=0.248        (e)          (e)      |               P=0.500        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    5/60 (8%)    2/60 (3%)    1/60 (2%)  |  0/60 (0%)    3/60 (5%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.1%        12.0%         6.3%         7.1%      |   0.0%         7.3%         2.2%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    2/34 (6%)    1/24 (4%)    0/9 (0%)   |  0/33 (0%)    3/41 (7%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      456 (I)      632          695       |   ---          728 (T)      533          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.600N     P=0.120      P=0.436      P=0.503    |  P=0.302N     P=0.162      P=0.500        (e)      |
|INCIDENTAL TUMOR       |  P=0.267N     P=0.101      P=0.451      P=0.708    |  P=0.273N     P=0.162      P=0.545        (e)      |
|LOGISTIC REGRESSION    |  P=0.324N     P=0.103      P=0.482      P=0.608    |  P=0.289N     P=0.162      P=0.541        (e)      |
|COCHRAN-ARMITAGE       |  P=0.271N                                          |  P=0.282N                                          |
|FISHER EXACT           |               P=0.103      P=0.500      P=0.752N   |               P=0.122      P=0.500        (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  18
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    1/60 (2%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         4.3%         0.0%         0.0%      |   0.0%         2.4%         2.2%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    0/24 (0%)    0/9 (0%)   |  0/33 (0%)    1/41 (2%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          456 (I)      ---          ---       |   ---          728 (T)      533          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.457N     P=0.246        (e)          (e)      |  P=0.552N     P=0.543      P=0.500        (e)      |
|INCIDENTAL TUMOR       |  P=0.326N     P=0.201        (e)          (e)      |  P=0.500N     P=0.543      P=0.545        (e)      |
|LOGISTIC REGRESSION    |  P=0.345N     P=0.261        (e)          (e)      |  P=0.538N     P=0.543      P=0.541        (e)      |
|COCHRAN-ARMITAGE       |  P=0.380N                                          |  P=0.540N                                          |
|FISHER EXACT           |               P=0.248        (e)          (e)      |               P=0.500      P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/59 (0%)    0/60 (0%)    2/60 (3%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.1%         0.0%         0.0%         9.7%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    0/34 (0%)    0/24 (0%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      ---          ---          518       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.064      P=0.488N     P=0.557N     P=0.260    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.275      P=0.488N     P=0.557N     P=0.566    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.179      P=0.488N     P=0.557N     P=0.468    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.193                                           |    (e)                                             |
|FISHER EXACT           |               P=0.504N     P=0.500N     P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  19
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    2/60 (3%)    2/60 (3%)  |  0/60 (0%)    1/60 (2%)    0/60 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         8.3%        15.3%      |   0.0%         2.3%         0.0%         6.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    2/24 (8%)    1/9 (11%)  |  0/33 (0%)    0/41 (0%)    0/26 (0%)    2/33 (6%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          728 (T)      663       |   ---          727          ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.007 **     (e)        P=0.177      P=0.066    |  P=0.137      P=0.553        (e)        P=0.238    |
|INCIDENTAL TUMOR       |  P=0.023 *      (e)        P=0.177      P=0.153    |  P=0.135      P=0.362        (e)        P=0.238    |
|LOGISTIC REGRESSION    |  P=0.029 *      (e)        P=0.177      P=0.133    |  P=0.136      P=0.543        (e)        P=0.238    |
|COCHRAN-ARMITAGE       |  P=0.124                                           |  P=0.149                                           |
|FISHER EXACT           |                 (e)        P=0.248      P=0.248    |               P=0.500        (e)        P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 53/60 (88%)  51/60 (85%)  54/60 (90%)  52/60 (87%) |                                                    |
|ADJUSTED (b)           |  96.3%        98.0%       100.0%       100.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  5/10 (50%)   6/10 (60%)   9/10 (90%)   7/9 (78%)  |                                                    |
|TERMINAL (d)           | 30/32 (94%)  33/34 (97%)  24/24 (100%)  9/9 (100%) |                                                    |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      456 (I)      456 (I)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.332N     P=0.078      P<0.001 ** |                                                    |
|INCIDENTAL TUMOR       |  P=0.173      P=0.511N     P=0.439      P=0.493    |                                                    |
|LOGISTIC REGRESSION    |  P=0.316      P=0.512N     P=0.465      P=0.421    |                                                    |
|COCHRAN-ARMITAGE       |  P=0.533N                                          |                                                    |
|FISHER EXACT           |               P=0.395N     P=0.500      P=0.500N   |                                                    |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  20
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    2/60 (3%)    2/60 (3%)    0/60 (0%)  |  5/60 (8%)    4/60 (7%)    2/60 (3%)    4/60 (7%)  |
|ADJUSTED (b)           |   3.1%         5.9%         6.1%         0.0%      |  15.2%         9.8%         7.7%        10.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |
|TERMINAL (d)           |  1/32 (3%)    2/34 (6%)    0/24 (0%)    0/9 (0%)   |  5/33 (15%)   4/41 (10%)   2/26 (8%)    2/33 (6%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      728 (T)      637          ---       |   728 (T)      728 (T)      728 (T)      458 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.548N     P=0.521      P=0.446      P=0.751N   |  P=0.564N     P=0.365N     P=0.319N     P=0.512N   |
|INCIDENTAL TUMOR       |  P=0.289N     P=0.521      P=0.545      P=0.751N   |  P=0.530N     P=0.365N     P=0.319N     P=0.461N   |
|LOGISTIC REGRESSION    |  P=0.388N     P=0.521      P=0.484      P=0.751N   |  P=0.541N     P=0.365N     P=0.319N     P=0.512N   |
|COCHRAN-ARMITAGE       |  P=0.246N                                          |  P=0.508N                                          |
|FISHER EXACT           |               P=0.506      P=0.506      P=0.496N   |               P=0.500N     P=0.219N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    2/60 (3%)    0/60 (0%)    1/60 (2%)  |  2/60 (3%)    2/60 (3%)    2/60 (3%)    2/60 (3%)  |
|ADJUSTED (b)           |   3.1%         5.4%         0.0%         2.5%      |   5.3%         4.9%         5.7%         3.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    1/10 (10%)   1/9 (11%)  |
|TERMINAL (d)           |  1/32 (3%)    1/34 (3%)    0/24 (0%)    0/9 (0%)   |  1/33 (3%)    2/41 (5%)    1/26 (4%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      655          ---          589       |   669          728 (T)      457 (I)      458 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.596      P=0.505      P=0.557N     P=0.609    |  P=0.582      P=0.628N     P=0.624      P=0.671    |
|INCIDENTAL TUMOR       |  P=0.568N     P=0.473      P=0.557N     P=0.776    |  P=0.607      P=0.695      P=0.629      P=0.671    |
|LOGISTIC REGRESSION    |  P=0.620N     P=0.498      P=0.557N     P=0.741    |  P=0.614N     P=0.667N     P=0.694      P=0.681N   |
|COCHRAN-ARMITAGE       |  P=0.555N                                          |  P=0.621                                           |
|FISHER EXACT           |               P=0.506      P=0.496N     P=0.748N   |               P=0.691N     P=0.691N     P=0.691N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  21
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/59 (3%)    4/60 (7%)    2/60 (3%)    1/60 (2%)  |  7/60 (12%)   6/60 (10%)   4/60 (7%)    6/60 (10%) |
|ADJUSTED (b)           |   6.3%        11.2%         6.1%         2.5%      |  20.1%        14.6%        13.3%        13.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    1/10 (10%)   2/9 (22%)  |
|TERMINAL (d)           |  2/32 (6%)    3/34 (9%)    0/24 (0%)    0/9 (0%)   |  6/33 (18%)   6/41 (15%)   3/26 (12%)   2/33 (6%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      655          637          589       |   669          728 (T)      457 (I)      458 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.611N     P=0.355      P=0.624      P=0.699    |  P=0.572      P=0.344N     P=0.399N     P=0.523N   |
|INCIDENTAL TUMOR       |  P=0.268N     P=0.333      P=0.686N     P=0.671N   |  P=0.533N     P=0.385N     P=0.396N     P=0.481N   |
|LOGISTIC REGRESSION    |  P=0.361N     P=0.337      P=0.673      P=0.609N   |  P=0.523N     P=0.398N     P=0.334N     P=0.502N   |
|COCHRAN-ARMITAGE       |  P=0.237N                                          |  P=0.506N                                          |
|FISHER EXACT           |               P=0.348      P=0.684N     P=0.494N   |               P=0.500N     P=0.264N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    1/60 (2%)    2/60 (3%)    0/60 (0%)  |  0/60 (0%)    2/60 (3%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.1%         2.2%         6.6%         0.0%      |   0.0%         4.7%         3.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    0/34 (0%)    1/24 (4%)    0/9 (0%)   |  0/33 (0%)    1/41 (2%)    1/26 (4%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      559          647          ---       |   ---          727          728 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.539N     P=0.758N     P=0.425      P=0.751N   |  P=0.412N     P=0.294      P=0.452        (e)      |
|INCIDENTAL TUMOR       |  P=0.324N     P=0.754N     P=0.494      P=0.751N   |  P=0.413N     P=0.186      P=0.452        (e)      |
|LOGISTIC REGRESSION    |  P=0.362N     P=0.757N     P=0.480      P=0.751N   |  P=0.409N     P=0.289      P=0.452        (e)      |
|COCHRAN-ARMITAGE       |  P=0.330N                                          |  P=0.385N                                          |
|FISHER EXACT           |               P=0.748N     P=0.506      P=0.496N   |               P=0.248      P=0.500        (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  22
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/59 (3%)    1/60 (2%)    2/60 (3%)    1/60 (2%)  |  0/60 (0%)    2/60 (3%)    2/60 (3%)    0/60 (0%)  |
|ADJUSTED (b)           |   6.3%         2.2%         6.6%         2.0%      |   0.0%         4.7%         6.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/32 (6%)    0/34 (0%)    1/24 (4%)    0/9 (0%)   |  0/33 (0%)    1/41 (2%)    1/26 (4%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      559          647          491       |   ---          727          630          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.587      P=0.491N     P=0.608      P=0.717    |  P=0.414N     P=0.294      P=0.199        (e)      |
|INCIDENTAL TUMOR       |  P=0.413N     P=0.486N     P=0.666      P=0.610N   |  P=0.354N     P=0.186      P=0.328        (e)      |
|LOGISTIC REGRESSION    |  P=0.487N     P=0.500N     P=0.669      P=0.528N   |  P=0.402N     P=0.289      P=0.220        (e)      |
|COCHRAN-ARMITAGE       |  P=0.473N                                          |  P=0.386N                                          |
|FISHER EXACT           |               P=0.494N     P=0.684N     P=0.494N   |               P=0.248      P=0.248        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 12/60 (20%)  13/60 (22%)   8/60 (13%)  11/60 (18%) |
|ADJUSTED (b)           |                                                    |  28.2%        30.8%        25.6%        27.8%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  3/10 (30%)   0/10 (0%)    0/10 (0%)    2/9 (22%)  |
|TERMINAL (d)           |                                                    |  7/33 (21%)  12/41 (29%)   5/26 (19%)   7/33 (21%) |
|FIRST INCIDENCE (DAYS) |                                                    |   438          646          533          457 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.522N     P=0.495N     P=0.369N     P=0.535N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.447N     P=0.586N     P=0.281N     P=0.489N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.444N     P=0.510      P=0.232N     P=0.492N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.424N                                          |
|FISHER EXACT           |                                                    |               P=0.500      P=0.232N     P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  23
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/60 (0%)    0/60 (0%)    3/60 (5%)    1/60 (2%)  |
|ADJUSTED (b)           |                                                    |   0.0%         0.0%         8.5%         2.5%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |                                                    |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          ---          459          647       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.370        (e)        P=0.097      P=0.486    |
|INCIDENTAL TUMOR       |                                                    |  P=0.390        (e)        P=0.105      P=0.429    |
|LOGISTIC REGRESSION    |                                                    |  P=0.393        (e)        P=0.131      P=0.501    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.387                                           |
|FISHER EXACT           |                                                    |                 (e)        P=0.122      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 12/60 (20%)  13/60 (22%)  11/60 (18%)  12/60 (20%) |
|ADJUSTED (b)           |                                                    |  28.2%        30.8%        31.9%        29.6%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  3/10 (30%)   0/10 (0%)    0/10 (0%)    2/9 (22%)  |
|TERMINAL (d)           |                                                    |  7/33 (21%)  12/41 (29%)   5/26 (19%)   7/33 (21%) |
|FIRST INCIDENCE (DAYS) |                                                    |   438          646          459          457 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.491      P=0.495N     P=0.513      P=0.551    |
|INCIDENTAL TUMOR       |                                                    |  P=0.539N     P=0.586N     P=0.572N     P=0.584    |
|LOGISTIC REGRESSION    |                                                    |  P=0.535N     P=0.510      P=0.493N     P=0.583N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.518N                                          |
|FISHER EXACT           |                                                    |               P=0.500      P=0.500N     P=0.590N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  24
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/60 (0%)    0/60 (0%)    2/60 (3%)  |  0/60 (0%)    1/60 (2%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   3.1%         0.0%         0.0%         9.7%      |   0.0%         2.4%         0.0%         3.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  1/32 (3%)    0/34 (0%)    0/24 (0%)    0/9 (0%)   |  0/33 (0%)    1/41 (2%)    0/26 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      ---          ---          518       |   ---          728 (T)      ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.064      P=0.488N     P=0.557N     P=0.260    |  P=0.440      P=0.543        (e)        P=0.500    |
|INCIDENTAL TUMOR       |  P=0.275      P=0.488N     P=0.557N     P=0.566    |  P=0.440      P=0.543        (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.177      P=0.488N     P=0.557N     P=0.468    |  P=0.440      P=0.543        (e)        P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.191                                           |  P=0.460                                           |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.500    |               P=0.500        (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/60 (0%)    0/60 (0%)    2/60 (3%)  |  1/60 (2%)    1/60 (2%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   6.3%         0.0%         0.0%         9.7%      |   3.0%         2.4%         0.0%         3.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  2/32 (6%)    0/34 (0%)    0/24 (0%)    0/9 (0%)   |  1/33 (3%)    1/41 (2%)    0/26 (0%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   728 (T)      ---          ---          518       |   728 (T)      728 (T)      ---          728 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.150      P=0.225N     P=0.303N     P=0.372    |  P=0.653      P=0.713N     P=0.548N     P=0.762    |
|INCIDENTAL TUMOR       |  P=0.400      P=0.225N     P=0.303N     P=0.656    |  P=0.653      P=0.713N     P=0.548N     P=0.762    |
|LOGISTIC REGRESSION    |  P=0.336      P=0.225N     P=0.303N     P=0.624    |  P=0.653      P=0.713N     P=0.548N     P=0.762    |
|COCHRAN-ARMITAGE       |  P=0.386                                           |  P=0.676                                           |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.691N   |               P=0.752N     P=0.500N     P=0.752N   |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  25
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 26/60 (43%)  26/60 (43%)  42/60 (70%)  36/60 (60%) | 14/60 (23%)  11/60 (18%)  15/60 (25%)  27/60 (45%) |
|ADJUSTED (b)           |  60.9%        60.7%        91.1%        89.4%      |  32.7%        24.6%        38.3%        59.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    2/9 (22%)  |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |
|TERMINAL (d)           | 16/32 (50%)  18/34 (53%)  20/24 (83%)   6/9 (67%)  |  6/33 (18%)   8/41 (20%)   5/26 (19%)  15/33 (45%) |
|FIRST INCIDENCE (DAYS) |   496          423          437          456 (I)   |   494          533          302          407       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.514N     P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.204N     P=0.285      P=0.017 *  |
|INCIDENTAL TUMOR       |  P=0.034 *    P=0.534      P=0.001 **   P=0.080    |  P<0.001 **   P=0.531N     P=0.557N     P=0.007 ** |
|LOGISTIC REGRESSION    |  P=0.024 *    P=0.543      P=0.001 **   P=0.104    |  P<0.001 **   P=0.596      P=0.460      P=0.008 ** |
|COCHRAN-ARMITAGE       |  P=0.031 *                                         |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.573N     P=0.003 **   P=0.050 *  |               P=0.327N     P=0.500      P=0.010 *  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/60 (0%)    1/60 (2%)    3/60 (5%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.6%         0.0%         4.2%         8.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |
|TERMINAL (d)           |  0/32 (0%)    0/34 (0%)    1/24 (4%)    0/9 (0%)   |  0/33 (0%)    0/41 (0%)    0/26 (0%)    0/33 (0%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      ---          728 (T)      502       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.112      P=0.244N     P=0.535N     P=0.438    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.450      P=0.240N     P=0.533N     P=0.497N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.248      P=0.142N     P=0.484N     P=0.656    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.187                                           |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.500N     P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  26
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 58/60 (97%)  54/60 (90%)  56/60 (93%)  55/60 (92%) | 43/60 (72%)  46/60 (77%)  41/60 (68%)  37/60 (62%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  89.3%        91.9%        88.6%        83.7%      |
|INTERIM SACRIFICE 1 (c)|  8/10 (80%)   6/10 (60%)   9/10 (90%)   7/9 (78%)  |  3/10 (30%)   2/10 (20%)   3/10 (30%)   2/9 (22%)  |
|TERMINAL (d)           | 32/32 (100%) 34/34 (100%) 24/24 (100%)  9/9 (100%) | 28/33 (85%)  37/41 (90%)  21/26 (81%)  26/33 (79%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      456 (I)      456 (I)   |   438          436          416          386       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.213N     P=0.146      P<0.001 ** |  P=0.271N     P=0.234N     P=0.210      P=0.238N   |
|INCIDENTAL TUMOR       |  P=0.424      P=0.195N     P=0.370N     P=0.454N   |  P=0.051N     P=0.341      P=0.575N     P=0.169N   |
|LOGISTIC REGRESSION    |  P=0.580N     P=0.195N     P=0.354N     P=0.415N   |  P=0.070N     P=0.388      P=0.572      P=0.177N   |
|COCHRAN-ARMITAGE       |  P=0.366N                                          |  P=0.065N                                          |
|FISHER EXACT           |               P=0.136N     P=0.340N     P=0.219N   |               P=0.339      P=0.421N     P=0.166N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 37/60 (62%)  35/60 (58%)  46/60 (77%)  47/60 (78%) | 21/60 (35%)  18/60 (30%)  30/60 (50%)  34/60 (57%) |
|ADJUSTED (b)           |  75.2%        74.0%        91.9%        97.4%      |  47.5%        39.0%        62.1%        71.7%      |
|INTERIM SACRIFICE 1 (c)|  2/10 (20%)   2/10 (20%)   1/10 (10%)   3/9 (33%)  |  0/10 (0%)    0/10 (0%)    3/10 (30%)   1/9 (11%)  |
|TERMINAL (d)           | 20/32 (63%)  22/34 (65%)  20/24 (83%)   8/9 (89%)  | 11/33 (33%)  13/41 (32%)   9/26 (35%)  20/33 (61%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      423          437          456 (I)   |   494          533          302          407       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.376N     P=0.016 *    P<0.001 ** |  P=0.003 **   P=0.173N     P=0.028 *    P=0.024 *  |
|INCIDENTAL TUMOR       |  P=0.038 *    P=0.530N     P=0.069      P=0.121    |  P=0.003 **   P=0.563N     P=0.167      P=0.013 *  |
|LOGISTIC REGRESSION    |  P=0.023 *    P=0.471N     P=0.048 *    P=0.111    |  P=0.003 **   P=0.566      P=0.108      P=0.010 ** |
|COCHRAN-ARMITAGE       |  P=0.012 *                                         |  P=0.002 **                                        |
|FISHER EXACT           |               P=0.426N     P=0.057      P=0.036 *  |               P=0.348N     P=0.070      P=0.014 *  |
|=================================================================================================================================|
 
         DATE: 09/12/94                     EXPERIMENT: 05092 TEST: 01                                                 PAGE  27
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- O-NITROANISOLE
 
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0%         0.0222%      0.0666%      0.200%    |   0.0%         0.0222%      0.0666%      0.200%    |
|                       |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |   15 SSAC      15 SSAC      15 SSAC      15 SSAC   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 58/60 (97%)  56/60 (93%)  59/60 (98%)  58/60 (97%) | 49/60 (82%)  48/60 (80%)  51/60 (85%)  50/60 (83%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  92.4%        96.0%        92.7%        94.3%      |
|INTERIM SACRIFICE 1 (c)|  8/10 (80%)   7/10 (70%)   9/10 (90%)   8/9 (89%)  |  3/10 (30%)   2/10 (20%)   5/10 (50%)   3/9 (33%)  |
|TERMINAL (d)           | 32/32 (100%) 34/34 (100%) 24/24 (100%)  9/9 (100%) | 29/33 (88%)  39/41 (95%)  22/26 (85%)  30/33 (91%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      423          437          456 (I)   |   438          436          302          386       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.323N     P=0.070      P<0.001 ** |  P=0.202      P=0.070N     P=0.079      P=0.442    |
|INCIDENTAL TUMOR       |  P=0.327      P=0.500N     P=0.500      P=0.539    |  P=0.533      P=0.605      P=0.494      P=0.600    |
|LOGISTIC REGRESSION    |  P=0.321      P=0.568N     P=0.456      P=0.539    |  P=0.335      P=0.438N     P=0.274      P=0.445    |
|COCHRAN-ARMITAGE       |  P=0.452                                           |  P=0.413                                           |
|FISHER EXACT           |               P=0.340N     P=0.500      P=0.691N   |               P=0.500N     P=0.404      P=0.500    |
|=================================================================================================================================|
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   456
          Female interim sacrifices(days): 456
 (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).