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TDMS Study 05092-03 Pathology Tables


NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                  O-NITROANISOLE                                    DATE: 04/08/97       
EXPERIMENT: 05092 TEST: 03                                                                                     TIME: 12:42:45       
TEST TYPE:  SPECIAL STUDY                       CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-45038                              ROUTE: DOSED FEED                                              NTP C#: 60388B       
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: 04/08/97       
EXPERIMENT: 05092 TEST: 03                                                                                     TIME: 12:42:45       
TEST TYPE:  SPECIAL STUDY                       CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-45038                              ROUTE: DOSED FEED                                              NTP C#: 60388B       
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 0091-23-6       
                                                    RATS(FISCHER 344)
                                              ----------------------------
             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
                                                    Adrenal Medulla
                                                    Brain
                                                    Clitoral Gland
                                                    Clitoral/Preputial Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                  O-NITROANISOLE                                    DATE: 04/08/97       
EXPERIMENT: 05092 TEST: 03                                                                                     TIME: 12:42:45       
TEST TYPE:  SPECIAL STUDY                       CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-45038                              ROUTE: DOSED FEED                                              NTP C#: 60388B       
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
              Intestine Large: Colon/Rectum Carcinoma
                                            Polyp Adenomatous
              Kidney: Pelvis and Transitional Epithelium
                                            Carcinoma
                                            Papilloma
              Stomach, Forestomach          Squamous Cell Papilloma
              Testes                        Adenoma
              Urinary Bladder               Carcinoma
                                            Carcinoma or Papilloma
                                            Papilloma
                                            Sarcoma
                                            Squamous Cell Carcinoma
                                            Squamous Cell Papilloma
              All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated
                                            Mesothelioma: Benign, Malignant, NOS
                                            Benign Tumors
                                            Malignant Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
                                                           FEMALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Intestine Large: Colon/Rectum Carcinoma
                                            Polyp Adenomatous
              Kidney: Pelvis and Transitional Epithelium
                                            Papilloma
              Mammary Gland                 Fibroadenoma
                                            Fibroma, Fibroadenoma or Adenoma
                                            Fibroma, Fibroadenoma, Carcinoma, or Adenoma
              Stomach, Forestomach          Squamous Cell Papilloma
              Urinary Bladder               Carcinoma
                                            Carcinoma or Papilloma
                                            Leiomyosarcoma
                                            Sarcoma
                                            Squamous Cell Papilloma
              All Organs                    Benign Tumors
                                            Malignant Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   1
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/2 (50%)       2/2 (100%)      0/0 (0%)       |     0/2 (0%)        0/0 (0%)        0/1 (0%)       |
|ADJUSTED (b)           |    100.0%           66.7%            0.0%          |      0.0%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 2 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 3 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 4 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|TERMINAL (d)           |     1/1 (100%)      0/0             0/0            |     0/1 (0%)        0/0             0/0            |
|FIRST INCIDENCE (DAYS) |      728 (T)         648             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.073         P=0.007 **        (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.760         P=0.362           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.760         P=0.362           (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.876                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=1.000N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/7 (14%)       1/7 (14%)       0/0 (0%)       |     2/5 (40%)       0/6 (0%)        0/1 (0%)       |
|ADJUSTED (b)           |     25.0%            8.3%            0.0%          |     36.4%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 2 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 3 (c)|     0/1 (0%)        0/1 (0%)        0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 4 (c)|     0/0             0/0             0/0            |     1/2 (50%)       0/1 (0%)        0/0            |
|TERMINAL (d)           |     1/4 (25%)       0/0             0/0            |     1/3 (33%)       0/2 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      728 (T)         480             ---           |      455 (I)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.781         P=0.398           (e)          |     P=0.653N        P=0.366N          (e)          |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.653N        P=0.366N          (e)          |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.341N        P=0.177N        P=0.688N       |
|COCHRAN-ARMITAGE       |     P=0.937                                        |     P=0.320N                                       |
|FISHER EXACT           |                     P=0.769N        P=1.000N       |                     P=0.182N        P=0.667N       |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   2
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/7 (29%)       1/7 (14%)       0/0 (0%)       |     2/5 (40%)       1/6 (17%)       0/1 (0%)       |
|ADJUSTED (b)           |     50.0%           16.7%            0.0%          |     66.7%           50.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 2 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 3 (c)|     0/1 (0%)        0/1 (0%)        0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 4 (c)|     0/0             0/0             0/0            |     0/2 (0%)        0/1 (0%)        0/0            |
|TERMINAL (d)           |     2/4 (50%)       0/0             0/0            |     2/3 (67%)       1/2 (50%)       0/0            |
|FIRST INCIDENCE (DAYS) |      728 (T)         636             ---           |      728 (T)         728 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.724         P=0.293           (e)          |     P=0.909N        P=0.691N          (e)          |
|INCIDENTAL TUMOR       |     P=0.921         P=0.638           (e)          |     P=0.909N        P=0.691N          (e)          |
|LOGISTIC REGRESSION    |     P=0.921         P=0.638           (e)          |     P=0.909N        P=0.691N          (e)          |
|COCHRAN-ARMITAGE       |     P=0.743N                                       |     P=0.420N                                       |
|FISHER EXACT           |                     P=0.500N        P=1.000N       |                     P=0.424N        P=0.667N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/7 (43%)       2/7 (29%)       0/0 (0%)       |     4/5 (80%)       1/6 (17%)       0/1 (0%)       |
|ADJUSTED (b)           |     75.0%           23.6%            0.0%          |    100.0%           50.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 2 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 3 (c)|     0/1 (0%)        0/1 (0%)        0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 4 (c)|     0/0             0/0             0/0            |     1/2 (50%)       0/1 (0%)        0/0            |
|TERMINAL (d)           |     3/4 (75%)       0/0             0/0            |     3/3 (100%)      1/2 (50%)       0/0            |
|FIRST INCIDENCE (DAYS) |      728 (T)         480             ---           |      455 (I)         728 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.289         P=0.093           (e)          |     P=0.539N        P=0.262N          (e)          |
|INCIDENTAL TUMOR       |     P=0.921         P=0.638           (e)          |     P=0.539N        P=0.262N          (e)          |
|LOGISTIC REGRESSION    |     P=0.921         P=0.638           (e)          |     P=0.276N        P=0.103N          (e)          |
|COCHRAN-ARMITAGE       |     P=0.712N                                       |     P=0.108N                                       |
|FISHER EXACT           |                     P=0.500N        P=1.000N       |                     P=0.067N        P=0.333N       |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   3
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large: Colon/Rectum                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/60 (0%)       0/60 (0%)       5/60 (8%)      |     0/60 (0%)       0/60 (0%)       2/60 (3%)      |
|ADJUSTED (b)           |      0.0%            0.0%           39.3%          |      0.0%            0.0%           19.8%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       1/6 (17%)      |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             ---             249           |      ---             ---             317           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **        (e)           P<0.001 **     |     P=0.010 *         (e)           P=0.053        |
|INCIDENTAL TUMOR       |     P=0.107           (e)           P=0.398        |     P=0.741           (e)           P=0.967        |
|LOGISTIC REGRESSION    |     P=0.005 **        (e)           P=0.036 *      |     P=0.079           (e)           P=0.202        |
|COCHRAN-ARMITAGE       |     P=0.004 **                                     |     P=0.092                                        |
|FISHER EXACT           |                       (e)           P=0.029 *      |                       (e)           P=0.248        |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large: Colon/Rectum                                                                                                    |
|     Polyp Adenomatous                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/60 (0%)      25/60 (42%)     30/60 (50%)     |     0/60 (0%)       8/60 (13%)     18/60 (30%)     |
|ADJUSTED (b)           |      0.0%           94.1%           95.5%          |      0.0%           51.4%          100.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       2/10 (20%)     |     0/10 (0%)       1/10 (10%)      0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       2/10 (20%)      4/6 (67%)      |     0/10 (0%)       0/10 (0%)       1/6 (17%)      |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        3/3 (100%)      0/0            |     0/8 (0%)        2/10 (20%)      0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             274 (I)         190 (I)       |      ---             190 (I)         233           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P=0.001 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P<0.001 **      P=0.003 **     |     P=0.024 *       P=0.012 *       P=0.078        |
|LOGISTIC REGRESSION    |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P=0.003 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P<0.001 **      P<0.001 **     |                     P=0.003 **      P<0.001 **     |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   4
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Pelvis and Transitional Epithelium                                                                                       |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/60 (0%)       1/60 (2%)       8/60 (13%)     |     0/60 (0%)       0/60 (0%)       1/60 (2%)      |
|ADJUSTED (b)           |      0.0%           33.3%           30.9%          |      0.0%            0.0%            6.3%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       2/6 (33%)      |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             648             217           |      ---             ---             307           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.174         P<0.001 **     |     P=0.194           (e)           P=0.381        |
|INCIDENTAL TUMOR       |     P=0.012 *       P=0.500         P=0.128        |     P=0.885           (e)           P=0.997        |
|LOGISTIC REGRESSION    |     P<0.001 **      P=0.313         P=0.010 **     |     P=0.299           (e)           P=0.504        |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P=0.296                                        |
|FISHER EXACT           |                     P=0.500         P=0.003 **     |                       (e)           P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Pelvis and Transitional Epithelium                                                                                       |
|     Papilloma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/60 (0%)       0/60 (0%)       4/60 (7%)      |     0/60 (0%)       0/60 (0%)       1/60 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%           23.1%          |      0.0%            0.0%           33.3%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       1/6 (17%)      |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             ---             228           |      ---             ---             346           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.001 **        (e)           P=0.016 *      |     P=0.029 *         (e)           P=0.082        |
|INCIDENTAL TUMOR       |     P=0.127           (e)           P=0.398        |     P=0.885           (e)           P=0.997        |
|LOGISTIC REGRESSION    |     P=0.017 *         (e)           P=0.084        |     P=0.268           (e)           P=0.468        |
|COCHRAN-ARMITAGE       |     P=0.011 *                                      |     P=0.296                                        |
|FISHER EXACT           |                       (e)           P=0.059        |                       (e)           P=0.500        |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   5
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/8 (25%)       0/7 (0%)        1/3 (33%)      |     0/3 (0%)        0/3 (0%)        0/2 (0%)       |
|ADJUSTED (b)           |     28.0%            0.0%            5.0%          |      0.0%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/0             0/0             0/1 (0%)       |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 2 (c)|     0/0             0/2 (0%)        0/0            |     0/0             0/2 (0%)        0/0            |
|INTERIM SACRIFICE 3 (c)|     0/0             0/2 (0%)        0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 4 (c)|     1/1 (100%)      0/0             0/0            |     0/0             0/0             0/0            |
|TERMINAL (d)           |     1/4 (25%)       0/0             0/0            |     0/1 (0%)        0/1 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      455 (I)         ---             263           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.182           (e)           P=0.362        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.638           (e)             (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.642         P=0.399N        P=0.925N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.656                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.267N        P=0.661        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/60 (2%)       0/60 (0%)       0/60 (0%)      |     8/60 (13%)      3/60 (5%)       0/60 (0%)      |
|ADJUSTED (b)           |      7.7%            0.0%            0.0%          |     48.3%           58.3%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     1/13 (8%)       0/1 (0%)        0/0            |     6/14 (43%)      2/4 (50%)       0/0            |
|FIRST INCIDENCE (DAYS) |      728 (T)         ---             ---           |      413             662             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=1.000N        P=0.952N          (e)          |     P=0.757         P=0.606         P=0.995N       |
|INCIDENTAL TUMOR       |     P=1.000N        P=0.952N          (e)          |     P=0.593N        P=0.575N        P=0.581N       |
|LOGISTIC REGRESSION    |     P=1.000N        P=0.952N          (e)          |     P=0.510N        P=0.448N        P=0.640N       |
|COCHRAN-ARMITAGE       |     P=0.394N                                       |     P=0.004N**                                     |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.102N        P=0.003N**     |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   6
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/60 (2%)       0/60 (0%)       0/60 (0%)      |     8/60 (13%)      3/60 (5%)       0/60 (0%)      |
|ADJUSTED (b)           |      7.7%            0.0%            0.0%          |     48.3%           58.3%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     1/13 (8%)       0/1 (0%)        0/0            |     6/14 (43%)      2/4 (50%)       0/0            |
|FIRST INCIDENCE (DAYS) |      728 (T)         ---             ---           |      413             662             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=1.000N        P=0.952N          (e)          |     P=0.757         P=0.606         P=0.995N       |
|INCIDENTAL TUMOR       |     P=1.000N        P=0.952N          (e)          |     P=0.593N        P=0.575N        P=0.581N       |
|LOGISTIC REGRESSION    |     P=1.000N        P=0.952N          (e)          |     P=0.510N        P=0.448N        P=0.640N       |
|COCHRAN-ARMITAGE       |     P=0.394N                                       |     P=0.004N**                                     |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.102N        P=0.003N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/60 (2%)       0/60 (0%)       0/60 (0%)      |     8/60 (13%)      3/60 (5%)       0/60 (0%)      |
|ADJUSTED (b)           |      7.7%            0.0%            0.0%          |     48.3%           58.3%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     1/13 (8%)       0/1 (0%)        0/0            |     6/14 (43%)      2/4 (50%)       0/0            |
|FIRST INCIDENCE (DAYS) |      728 (T)         ---             ---           |      413             662             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=1.000N        P=0.952N          (e)          |     P=0.757         P=0.606         P=0.995N       |
|INCIDENTAL TUMOR       |     P=1.000N        P=0.952N          (e)          |     P=0.593N        P=0.575N        P=0.581N       |
|LOGISTIC REGRESSION    |     P=1.000N        P=0.952N          (e)          |     P=0.510N        P=0.448N        P=0.640N       |
|COCHRAN-ARMITAGE       |     P=0.394N                                       |     P=0.004N**                                     |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.102N        P=0.003N**     |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   7
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/8 (88%)       0/0 (0%)        0/0 (0%)       |    12/13 (92%)      5/9 (56%)       0/0 (0%)       |
|ADJUSTED (b)           |     83.1%            0.0%            0.0%          |    100.0%           77.4%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 2 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 3 (c)|     0/0             0/0             0/0            |     0/0             0/0             0/0            |
|INTERIM SACRIFICE 4 (c)|     1/1 (100%)      0/0             0/0            |     0/0             1/1 (100%)      0/0            |
|TERMINAL (d)           |     4/5 (80%)       0/0             0/0            |     9/9 (100%)      2/3 (67%)       0/0            |
|FIRST INCIDENCE (DAYS) |      455 (I)         ---             ---           |      648             455 (I)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.876N        P=0.584N          (e)          |     P=0.812N        P=0.661N          (e)          |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.296N        P=0.097N          (e)          |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.296N        P=0.097N          (e)          |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.162N                                       |
|FISHER EXACT           |                     P=1.000N        P=1.000N       |                     P=0.067N        P=1.000N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal                                                       |
|     Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepithelioma                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/60 (5%)       0/60 (0%)       0/60 (0%)      |     1/60 (2%)       0/60 (0%)       0/60 (0%)      |
|ADJUSTED (b)           |     16.8%            0.0%            0.0%          |      5.6%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     1/9 (11%)       0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     1/13 (8%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      455 (I)         ---             ---           |      590             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.865N        P=0.582N          (e)          |     P=0.910N        P=0.617N          (e)          |
|INCIDENTAL TUMOR       |     P=0.599N        P=0.325N          (e)          |     P=0.673N        P=0.186N          (e)          |
|LOGISTIC REGRESSION    |     P=0.381N        P=0.260N        P=0.730N       |     P=0.686N        P=0.571N        P=0.897N       |
|COCHRAN-ARMITAGE       |     P=0.081N                                       |     P=0.394N                                       |
|FISHER EXACT           |                     P=0.122N        P=0.122N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   8
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/60 (3%)       0/60 (0%)       0/60 (0%)      |     0/60 (0%)       0/60 (0%)       0/60 (0%)      |
|ADJUSTED (b)           |     13.8%            0.0%            0.0%          |      0.0%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     1/13 (8%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      701             ---             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.993N        P=0.850N          (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.777N        P=0.449N          (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.953N        P=0.687N          (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.171N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.248N        P=0.248N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/60 (3%)       0/60 (0%)       0/60 (0%)      |     0/60 (0%)       0/60 (0%)       0/60 (0%)      |
|ADJUSTED (b)           |     10.9%            0.0%            0.0%          |      0.0%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     1/9 (11%)       0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     1/13 (8%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      455 (I)         ---             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.911N        P=0.638N          (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.911N        P=0.638N          (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.464N        P=0.362N        P=0.738N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.171N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.248N        P=0.248N       |                       (e)             (e)          |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE   9
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/60 (5%)       0/60 (0%)       0/60 (0%)      |     1/60 (2%)       0/60 (0%)       0/60 (0%)      |
|ADJUSTED (b)           |     16.8%            0.0%            0.0%          |      5.6%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     1/9 (11%)       0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     1/13 (8%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      455 (I)         ---             ---           |      590             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.865N        P=0.582N          (e)          |     P=0.910N        P=0.617N          (e)          |
|INCIDENTAL TUMOR       |     P=0.599N        P=0.325N          (e)          |     P=0.673N        P=0.186N          (e)          |
|LOGISTIC REGRESSION    |     P=0.381N        P=0.260N        P=0.730N       |     P=0.686N        P=0.571N        P=0.897N       |
|COCHRAN-ARMITAGE       |     P=0.081N                                       |     P=0.394N                                       |
|FISHER EXACT           |                     P=0.122N        P=0.122N       |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/60 (5%)       0/60 (0%)       0/60 (0%)      |     0/60 (0%)       0/60 (0%)       0/60 (0%)      |
|ADJUSTED (b)           |     16.8%            0.0%            0.0%          |      0.0%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     1/9 (11%)       0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     1/13 (8%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      455 (I)         ---             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.865N        P=0.582N          (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.599N        P=0.325N          (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.381N        P=0.260N        P=0.730N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.081N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.122N        P=0.122N       |                       (e)             (e)          |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  10
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/60 (0%)       4/60 (7%)       1/60 (2%)      |     1/60 (2%)       4/60 (7%)       4/60 (7%)      |
|ADJUSTED (b)           |      0.0%           29.7%           16.7%          |      7.1%           48.1%          100.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       1/10 (10%)      0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     1/14 (7%)       1/4 (25%)       0/0            |
|FIRST INCIDENCE (DAYS) |      ---             190 (I)         298           |      728 (T)         424             245           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.045 *       P=0.018 *       P=0.186        |     P<0.001 **      P=0.026 *       P<0.001 **     |
|INCIDENTAL TUMOR       |     P=0.602         P=0.233           (e)          |     P=0.074         P=0.120         P=0.368        |
|LOGISTIC REGRESSION    |     P=0.427         P=0.048 *       P=0.510        |     P=0.005 **      P=0.059         P=0.040 *      |
|COCHRAN-ARMITAGE       |     P=0.596                                        |     P=0.205                                        |
|FISHER EXACT           |                     P=0.059         P=0.500        |                     P=0.182         P=0.182        |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    26/60 (43%)     23/60 (38%)      0/60 (0%)      |                                                    |
|ADJUSTED (b)           |    100.0%          100.0%            0.0%          |                                                    |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |                                                    |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |                                                    |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |                                                    |
|INTERIM SACRIFICE 4 (c)|     6/9 (67%)       3/3 (100%)      0/0            |                                                    |
|TERMINAL (d)           |    13/13 (100%)     1/1 (100%)      0/0            |                                                    |
|FIRST INCIDENCE (DAYS) |      455 (I)         329             ---           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P<0.001 **        (e)          |                                                    |
|INCIDENTAL TUMOR       |     P=0.799N        P=0.086           (e)          |                                                    |
|LOGISTIC REGRESSION    |     P=0.436         P=0.050 *         (e)          |                                                    |
|COCHRAN-ARMITAGE       |     P<0.001N**                                     |                                                    |
|FISHER EXACT           |                     P=0.355N        P<0.001N**     |                                                    |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  11
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/59 (0%)      27/59 (46%)     50/60 (83%)     |     0/58 (0%)      28/59 (47%)     48/60 (80%)     |
|ADJUSTED (b)           |      0.0%          100.0%          100.0%          |      0.0%          100.0%          100.0%          |
|INTERIM SACRIFICE 1 (c)|     0/9 (0%)        0/9 (0%)        1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)      10/10 (100%)    |     0/10 (0%)       0/10 (0%)      10/10 (100%)    |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       3/10 (30%)      6/6 (100%)     |     0/10 (0%)       1/9 (11%)       6/6 (100%)     |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        1/3 (33%)       0/0            |     0/8 (0%)        9/10 (90%)      0/0            |
|TERMINAL (d)           |     0/13 (0%)       1/1 (100%)      0/0            |     0/12 (0%)       4/4 (100%)      0/0            |
|FIRST INCIDENCE (DAYS) |      ---             274 (I)          87 (I)       |      ---             274 (I)         190 (I)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P<0.001 **      P<0.001 **     |                     P<0.001 **      P<0.001 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Carcinoma or Papilloma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/59 (0%)      36/59 (61%)     50/60 (83%)     |     0/58 (0%)      30/59 (51%)     48/60 (80%)     |
|ADJUSTED (b)           |      0.0%          100.0%          100.0%          |      0.0%          100.0%          100.0%          |
|INTERIM SACRIFICE 1 (c)|     0/9 (0%)        0/9 (0%)        1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       2/10 (20%)     10/10 (100%)    |     0/10 (0%)       0/10 (0%)      10/10 (100%)    |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       5/10 (50%)      6/6 (100%)     |     0/10 (0%)       1/9 (11%)       6/6 (100%)     |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        3/3 (100%)      0/0            |     0/8 (0%)       10/10 (100%)     0/0            |
|TERMINAL (d)           |     0/13 (0%)       1/1 (100%)      0/0            |     0/12 (0%)       4/4 (100%)      0/0            |
|FIRST INCIDENCE (DAYS) |      ---             190 (I)          87 (I)       |      ---             274 (I)         190 (I)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P<0.001 **      P<0.001 **     |                     P<0.001 **      P<0.001 **     |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  12
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Leiomyosarcoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/59 (0%)       0/59 (0%)       0/60 (0%)      |     0/58 (0%)       1/59 (2%)       2/60 (3%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      0.0%            7.1%           22.2%          |
|INTERIM SACRIFICE 1 (c)|     0/9 (0%)        0/9 (0%)        0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/9 (0%)        0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/12 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      ---             476             333           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.003 **      P=0.450         P=0.038 *      |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.696         P=0.669         P=0.967        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.108         P=0.485         P=0.194        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.182                                        |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.504         P=0.256        |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Papilloma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/59 (0%)       9/59 (15%)      1/60 (2%)      |     0/58 (0%)       2/59 (3%)       1/60 (2%)      |
|ADJUSTED (b)           |      0.0%           53.8%            3.3%          |      0.0%           12.2%            3.4%          |
|INTERIM SACRIFICE 1 (c)|     0/9 (0%)        0/9 (0%)        0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       2/10 (20%)      0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       2/10 (20%)      0/6 (0%)       |     0/10 (0%)       0/9 (0%)        0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        2/3 (67%)       0/0            |     0/8 (0%)        1/10 (10%)      0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/12 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             190 (I)         236           |      ---             455 (I)         265           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.101         P<0.001 **      P=0.443        |     P=0.087         P=0.218         P=0.441        |
|INCIDENTAL TUMOR       |     P=0.394         P=0.002 **        (e)          |     P=0.636         P=0.359         P=0.997        |
|LOGISTIC REGRESSION    |     P=0.586N        P=0.002 **      P=0.570        |     P=0.384         P=0.219         P=0.536        |
|COCHRAN-ARMITAGE       |     P=0.456N                                       |     P=0.509                                        |
|FISHER EXACT           |                     P=0.001 **      P=0.504        |                     P=0.252         P=0.508        |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  13
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/59 (0%)       2/59 (3%)       9/60 (15%)     |     0/58 (0%)       1/59 (2%)      11/60 (18%)     |
|ADJUSTED (b)           |      0.0%            9.6%           68.0%          |      0.0%            8.3%          100.0%          |
|INTERIM SACRIFICE 1 (c)|     0/9 (0%)        0/9 (0%)        0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       2/10 (20%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/9 (0%)        2/6 (33%)      |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        1/3 (33%)       0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/12 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             305             158           |      ---             504             248           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.123         P<0.001 **     |     P<0.001 **      P=0.419         P<0.001 **     |
|INCIDENTAL TUMOR       |     P=0.074         P=0.282         P=0.234        |     P=0.009 **      P=0.669         P=0.043 *      |
|LOGISTIC REGRESSION    |     P=0.001 **      P=0.231         P=0.009 **     |     P<0.001 **      P=0.478         P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.248         P=0.002 **     |                     P=0.504         P<0.001 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/59 (0%)       0/59 (0%)       6/60 (10%)     |     0/58 (0%)       0/59 (0%)       1/60 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%           67.5%          |      0.0%            0.0%            9.1%          |
|INTERIM SACRIFICE 1 (c)|     0/9 (0%)        0/9 (0%)        0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       1/6 (17%)      |     0/10 (0%)       0/9 (0%)        0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/12 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             ---             242           |      ---             ---             324           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **        (e)           P<0.001 **     |     P=0.141           (e)           P=0.307        |
|INCIDENTAL TUMOR       |     P=0.090           (e)           P=0.398        |     P=0.885           (e)           P=0.997        |
|LOGISTIC REGRESSION    |     P=0.002 **        (e)           P=0.020 *      |     P=0.289           (e)           P=0.490        |
|COCHRAN-ARMITAGE       |     P=0.001 **                                     |     P=0.301                                        |
|FISHER EXACT           |                       (e)           P=0.014 *      |                       (e)           P=0.508        |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  14
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/59 (0%)       0/59 (0%)       4/60 (7%)      |     0/58 (0%)       0/59 (0%)       4/60 (7%)      |
|ADJUSTED (b)           |      0.0%            0.0%           63.1%          |      0.0%            0.0%           34.2%          |
|INTERIM SACRIFICE 1 (c)|     0/9 (0%)        0/9 (0%)        0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/9 (0%)        0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/12 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             ---             254           |      ---             ---             221           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **        (e)           P<0.001 **     |     P<0.001 **        (e)           P=0.006 **     |
|INCIDENTAL TUMOR       |     P=0.400           (e)             (e)          |     P=0.562           (e)           P=0.877        |
|LOGISTIC REGRESSION    |     P=0.012 *         (e)           P=0.062        |     P=0.013 *         (e)           P=0.062        |
|COCHRAN-ARMITAGE       |     P=0.011 *                                      |     P=0.012 *                                      |
|FISHER EXACT           |                       (e)           P=0.061        |                       (e)           P=0.064        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     3/60 (5%)       3/60 (5%)       0/60 (0%)      |
|ADJUSTED (b)           |                                                    |     17.6%           22.1%            0.0%          |
|INTERIM SACRIFICE 1 (c)|                                                    |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|                                                    |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|                                                    |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|                                                    |     1/8 (13%)       1/10 (10%)      0/0            |
|TERMINAL (d)           |                                                    |     2/14 (14%)      0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |                                                    |      455 (I)         455 (I)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.610         P=0.434           (e)          |
|INCIDENTAL TUMOR       |                                                    |     P=0.651N        P=0.650N          (e)          |
|LOGISTIC REGRESSION    |                                                    |     P=0.487N        P=0.515         P=0.700N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.091N                                       |
|FISHER EXACT           |                                                    |                     P=0.660N        P=0.122N       |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  15
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/60 (0%)       2/60 (3%)       0/60 (0%)      |     0/60 (0%)       0/60 (0%)       0/60 (0%)      |
|ADJUSTED (b)           |      0.0%           16.7%            0.0%          |      0.0%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             275             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.561         P=0.150           (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.387N        P=0.581           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.763         P=0.199           (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.575N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.248           (e)          |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    12/60 (20%)      2/60 (3%)       0/60 (0%)      |     3/60 (5%)       0/60 (0%)       0/60 (0%)      |
|ADJUSTED (b)           |     62.9%           41.7%            0.0%          |     20.0%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        0/3 (0%)        0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     6/13 (46%)      0/1 (0%)        0/0            |     2/14 (14%)      0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      564             617             ---           |      679             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.772N        P=0.630N          (e)          |     P=0.689N        P=0.413N          (e)          |
|INCIDENTAL TUMOR       |     P=0.053N        P=0.020N*         (e)          |     P=0.582N        P=0.323N          (e)          |
|LOGISTIC REGRESSION    |     P=0.212N        P=0.140N        P=0.724N       |     P=0.581N        P=0.314N        P=1.000N       |
|COCHRAN-ARMITAGE       |     P<0.001N**                                     |     P=0.081N                                       |
|FISHER EXACT           |                     P=0.004N**      P<0.001N**     |                     P=0.122N        P=0.122N       |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  16
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma: Benign, Malignant, NOS                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/60 (0%)       6/60 (10%)      0/60 (0%)      |     0/60 (0%)       0/60 (0%)       0/60 (0%)      |
|ADJUSTED (b)           |      0.0%           46.9%            0.0%          |      0.0%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       0/10 (0%)       0/6 (0%)       |     0/10 (0%)       0/10 (0%)       0/6 (0%)       |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        2/3 (67%)       0/0            |     0/8 (0%)        0/10 (0%)       0/0            |
|TERMINAL (d)           |     0/13 (0%)       0/1 (0%)        0/0            |     0/14 (0%)       0/4 (0%)        0/0            |
|FIRST INCIDENCE (DAYS) |      ---             423             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.002 **      P<0.001 **        (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.055         P=0.018 *         (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.084         P=0.005 **        (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.370N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.014 *         (e)          |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    26/60 (43%)     35/60 (58%)     32/60 (53%)     |    18/60 (30%)     18/60 (30%)     22/60 (37%)     |
|ADJUSTED (b)           |    100.0%          100.0%           96.4%          |     89.5%           93.6%          100.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       3/10 (30%)      2/10 (20%)     |     0/10 (0%)       1/10 (10%)      0/10 (0%)      |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       4/10 (40%)      4/6 (67%)      |     0/10 (0%)       0/10 (0%)       1/6 (17%)      |
|INTERIM SACRIFICE 4 (c)|     6/9 (67%)       3/3 (100%)      0/0            |     2/8 (25%)       3/10 (30%)      0/0            |
|TERMINAL (d)           |    13/13 (100%)     1/1 (100%)      0/0            |    12/14 (86%)      3/4 (75%)       0/0            |
|FIRST INCIDENCE (DAYS) |      455 (I)         190 (I)         190 (I)       |      413             190 (I)         221           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P=0.007 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P=0.006 **      P<0.001 **      P=0.003 **     |     P=0.126         P=0.198         P=0.154        |
|LOGISTIC REGRESSION    |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P=0.166         P<0.001 **     |
|COCHRAN-ARMITAGE       |     P=0.237                                        |     P=0.234                                        |
|FISHER EXACT           |                     P=0.072         P=0.181        |                     P=0.579N        P=0.281        |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  17
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      0.0%            0.600%          1.80%         |      0.0%            0.600%          1.80%         |
|                       |      15 SSAC         15 SSAC         15 SSAC       |      15 SSAC         15 SSAC         15 SSAC       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/60 (25%)     32/60 (53%)     51/60 (85%)     |    10/60 (17%)     30/60 (50%)     48/60 (80%)     |
|ADJUSTED (b)           |     75.0%          100.0%          100.0%          |     53.2%          100.0%          100.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)      10/10 (100%)    |     0/10 (0%)       0/10 (0%)      10/10 (100%)    |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       3/10 (30%)      6/6 (100%)     |     0/10 (0%)       1/10 (10%)      6/6 (100%)     |
|INTERIM SACRIFICE 4 (c)|     0/9 (0%)        3/3 (100%)      0/0            |     0/8 (0%)        9/10 (90%)      0/0            |
|TERMINAL (d)           |     8/13 (62%)      1/1 (100%)      0/0            |     6/14 (43%)      4/4 (100%)      0/0            |
|FIRST INCIDENCE (DAYS) |      564             207              87 (I)       |      408             274 (I)         190 (I)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.001 **      P<0.001 **     |                     P<0.001 **      P<0.001 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    26/60 (43%)     39/60 (65%)     51/60 (85%)     |    22/60 (37%)     32/60 (53%)     48/60 (80%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     95.4%          100.0%          100.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       3/10 (30%)     10/10 (100%)    |     0/10 (0%)       1/10 (10%)     10/10 (100%)    |
|INTERIM SACRIFICE 3 (c)|     0/10 (0%)       6/10 (60%)      6/6 (100%)     |     0/10 (0%)       1/10 (10%)      6/6 (100%)     |
|INTERIM SACRIFICE 4 (c)|     6/9 (67%)       3/3 (100%)      0/0            |     2/8 (25%)      10/10 (100%)     0/0            |
|TERMINAL (d)           |    13/13 (100%)     1/1 (100%)      0/0            |    13/14 (93%)      4/4 (100%)      0/0            |
|FIRST INCIDENCE (DAYS) |      455 (I)         190 (I)          87 (I)       |      408             190 (I)         190 (I)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.014 *       P<0.001 **     |                     P=0.049 *       P<0.001 **     |
|=================================================================================================================================|
         DATE: 04/08/97                     EXPERIMENT: 05092 TEST: 03                                                 PAGE  18
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER 344) -- O-NITROANISOLE
                                                 TERMINAL SACRIFICE AT 104 WEEKS
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   87  190  274  455
          Female interim sacrifices(days): 87  190  274  455
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).