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TDMS Study 05043-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                          2,4-DIAMINOPHENOL DIHYDROCHLORIDE                          DATE: 09/05/94       
EXPERIMENT: 05043 TEST: 01                                                                                     TIME: 17:53:48       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 60026        
PATHOLOGIST: S. WYAND                        S. EUSTIS                                                         CAS: 137-09-7        
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Mason                                          2,4-DIAMINOPHENOL DIHYDROCHLORIDE                          DATE: 09/05/94      
EXPERIMENT: 05043 TEST: 01                                                                                     TIME: 17:53:48      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 60026       
PATHOLOGIST: S. WYAND                        S. EUSTIS                                                         CAS: 137-09-7       
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                          2,4-DIAMINOPHENOL DIHYDROCHLORIDE                          DATE: 09/05/94       
EXPERIMENT: 05043 TEST: 01                                                                                     TIME: 17:53:48       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01CP9561903          ROUTE: GAVAGE                                                                      NTP C#: 60026        
PATHOLOGIST: S. WYAND                        S. EUSTIS                                                         CAS: 137-09-7        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                               IN THE ANALYSIS OF THE STUDY OF 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Islets, Pancreatic            Adenoma
                                                           Carcinoma or Adenoma
                             Mammary Gland                 Fibroadenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Testes                        Adenoma
                             Thyroid Gland: C-Cell         Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Islets, Pancreatic            Adenoma
                                                           Carcinoma or Adenoma
                             Mammary Gland                 Carcinoma
                             Pancreas                      Adenoma
                             Skin: Subcutaneous Tissue     Fibrosarcoma
                                                           Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, or Sarcoma
                             Uterus                        Polyp Stromal
                             All Organs                    Malignant Tumors
 
              ====================================================================================================
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   1
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    10/49 (20%)      8/50 (16%)      7/50 (14%)     |     2/48 (4%)       1/15 (7%)       3/48 (6%)      |
|ADJUSTED (b)           |     35.2%           36.2%           33.5%          |      6.9%           50.0%            8.4%          |
|TERMINAL (d)           |     7/24 (29%)      7/21 (33%)      4/16 (25%)     |     2/29 (7%)       1/2 (50%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      570             687             468           |      729 (T)         729 (T)         645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.547N        P=0.532N        P=0.596N       |     P=0.441         P=0.228         P=0.528        |
|INCIDENTAL TUMOR       |     P=0.470N        P=0.557N        P=0.492N       |     P=0.437         P=0.228         P=0.518        |
|LOGISTIC REGRESSION    |     P=0.421N        P=0.563N        P=0.442N       |     P=0.427         P=0.228         P=0.514        |
|COCHRAN-ARMITAGE       |     P=0.237N                                       |     P=0.411                                        |
|FISHER EXACT           |                     P=0.379N        P=0.282N       |                     P=0.564         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/49 (14%)      2/50 (4%)       3/50 (6%)      |     0/48 (0%)       0/15 (0%)       0/48 (0%)      |
|ADJUSTED (b)           |     24.8%            9.5%           15.6%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     5/24 (21%)      2/21 (10%)      2/16 (13%)     |     0/29 (0%)       0/2 (0%)        0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      525             729 (T)         644           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.217N        P=0.120N        P=0.336N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.165N        P=0.114N        P=0.247N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.155N        P=0.117N        P=0.229N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.093N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.075N        P=0.151N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   2
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/49 (31%)      9/50 (18%)      9/50 (18%)     |     2/48 (4%)       1/15 (7%)       3/48 (6%)      |
|ADJUSTED (b)           |     49.4%           40.8%           41.2%          |      6.9%           50.0%            8.4%          |
|TERMINAL (d)           |    10/24 (42%)      8/21 (38%)      5/16 (31%)     |     2/29 (7%)       1/2 (50%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      525             687             468           |      729 (T)         729 (T)         645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.338N        P=0.217N        P=0.413N       |     P=0.441         P=0.228         P=0.528        |
|INCIDENTAL TUMOR       |     P=0.233N        P=0.222N        P=0.258N       |     P=0.437         P=0.228         P=0.518        |
|LOGISTIC REGRESSION    |     P=0.198N        P=0.222N        P=0.219N       |     P=0.427         P=0.228         P=0.514        |
|COCHRAN-ARMITAGE       |     P=0.083N                                       |     P=0.411                                        |
|FISHER EXACT           |                     P=0.109N        P=0.109N       |                     P=0.564         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/17 (6%)       2/24 (8%)       2/26 (8%)      |     2/12 (17%)      1/17 (6%)       1/9 (11%)      |
|ADJUSTED (b)           |     50.0%            5.9%           36.0%          |     66.7%           14.3%           50.0%          |
|TERMINAL (d)           |     1/2 (50%)       0/2 (0%)        1/3 (33%)      |     2/3 (67%)       1/7 (14%)       1/2 (50%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         488             653           |      729 (T)         729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.405         P=0.453         P=0.563        |     P=0.439N        P=0.196N        P=0.691N       |
|INCIDENTAL TUMOR       |     P=0.498         P=0.562         P=0.601        |     P=0.439N        P=0.196N        P=0.691N       |
|LOGISTIC REGRESSION    |     P=0.509         P=0.534         P=0.628        |     P=0.439N        P=0.196N        P=0.691N       |
|COCHRAN-ARMITAGE       |     P=0.540                                        |     P=0.448N                                       |
|FISHER EXACT           |                     P=0.630         P=0.658        |                     P=0.367N        P=0.612N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   3
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/17 (12%)      3/24 (13%)      2/26 (8%)      |     1/12 (8%)       5/17 (29%)      1/9 (11%)      |
|ADJUSTED (b)           |      4.8%           53.2%            8.3%          |     33.3%           45.6%            2.6%          |
|TERMINAL (d)           |     0/2 (0%)        1/2 (50%)       0/3 (0%)       |     1/3 (33%)       3/7 (43%)       0/2 (0%)       |
|FIRST INCIDENCE (DAYS) |      525             581             632           |      729 (T)         540             676           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.531         P=0.445         P=0.611        |     P=0.539         P=0.244         P=0.716        |
|INCIDENTAL TUMOR       |     P=0.529N        P=0.514         P=0.642N       |     P=0.424N        P=0.443         P=0.581N       |
|LOGISTIC REGRESSION    |     P=0.446N        P=0.549         P=0.570N       |     P=0.546         P=0.378         P=0.732        |
|COCHRAN-ARMITAGE       |     P=0.412N                                       |     P=0.488                                        |
|FISHER EXACT           |                     P=0.665         P=0.521N       |                     P=0.182         P=0.686        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/17 (18%)      5/24 (21%)      4/26 (15%)     |     3/12 (25%)      6/17 (35%)      2/9 (22%)      |
|ADJUSTED (b)           |     52.4%           56.0%           41.3%          |    100.0%           59.2%           51.3%          |
|TERMINAL (d)           |     1/2 (50%)       1/2 (50%)       1/3 (33%)      |     3/3 (100%)      4/7 (57%)       1/2 (50%)      |
|FIRST INCIDENCE (DAYS) |      525             488             632           |      729 (T)         540             676           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.391         P=0.287         P=0.470        |     P=0.536N        P=0.651         P=0.716N       |
|INCIDENTAL TUMOR       |     P=0.556         P=0.399         P=0.617        |     P=0.247N        P=0.513N        P=0.419N       |
|LOGISTIC REGRESSION    |     P=0.542N        P=0.397         P=0.674N       |     P=0.518N        P=0.557N        P=0.708N       |
|COCHRAN-ARMITAGE       |     P=0.482N                                       |     P=0.571N                                       |
|FISHER EXACT           |                     P=0.563         P=0.581N       |                     P=0.432         P=0.647N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   4
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       3/22 (14%)      2/50 (4%)      |     0/49 (0%)       1/14 (7%)       0/50 (0%)      |
|ADJUSTED (b)           |     10.1%          100.0%           12.5%          |      0.0%          100.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       2/2 (100%)      2/16 (13%)     |     0/29 (0%)       1/1 (100%)      0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      570             653             729 (T)       |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.543         P=0.169         P=0.655N       |     P=0.681N        P=0.005 **        (e)          |
|INCIDENTAL TUMOR       |     P=0.575N        P=0.017 *       P=0.605N       |     P=0.681N        P=0.005 **        (e)          |
|LOGISTIC REGRESSION    |     P=0.548N        P=0.017 *       P=0.588N       |     P=0.681N        P=0.005 **        (e)          |
|COCHRAN-ARMITAGE       |     P=0.420N                                       |     P=0.701N                                       |
|FISHER EXACT           |                     P=0.259         P=0.500N       |                     P=0.222           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       3/22 (14%)      2/50 (4%)      |     0/49 (0%)       2/14 (14%)      0/50 (0%)      |
|ADJUSTED (b)           |     14.0%          100.0%           12.5%          |      0.0%          100.0%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       2/2 (100%)      2/16 (13%)     |     0/29 (0%)       1/1 (100%)      0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      570             653             729 (T)       |      ---             653             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.489N        P=0.197         P=0.511N       |     P=0.641N        P=0.032 *         (e)          |
|INCIDENTAL TUMOR       |     P=0.453N        P=0.026 *       P=0.462N       |     P=0.620N        P<0.001 **        (e)          |
|LOGISTIC REGRESSION    |     P=0.419N        P=0.025 *       P=0.436N       |     P=0.633N        P=0.002 **        (e)          |
|COCHRAN-ARMITAGE       |     P=0.283N                                       |     P=0.643N                                       |
|FISHER EXACT           |                     P=0.363         P=0.339N       |                     P=0.047 *         (e)          |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   5
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/30 (0%)       3/50 (6%)      |     1/50 (2%)       1/17 (6%)       0/50 (0%)      |
|ADJUSTED (b)           |      8.3%            0.0%           14.2%          |      3.3%            2.6%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       0/5 (0%)        1/16 (6%)      |     1/30 (3%)       0/3 (0%)        0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             632           |      729 (T)         625             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.270         P=0.616N        P=0.350        |     P=0.341N        P=0.550         P=0.493N       |
|INCIDENTAL TUMOR       |     P=0.303         P=0.616N        P=0.395        |     P=0.331N        P=0.716         P=0.493N       |
|LOGISTIC REGRESSION    |     P=0.303         P=0.616N        P=0.391        |     P=0.347N        P=0.449         P=0.493N       |
|COCHRAN-ARMITAGE       |     P=0.397                                        |     P=0.350N                                       |
|FISHER EXACT           |                     P=0.388N        P=0.500        |                     P=0.446         P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     3/50 (6%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      7.4%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/21 (0%)       0/16 (0%)      |     1/30 (3%)       0/32 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      199             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.036N*       P=0.115N        P=0.120N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.058N        P=0.133N        P=0.168N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.077N        P=0.202N        P=0.201N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.037N*                                      |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.121N        P=0.121N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   6
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       0/50 (0%)       0/50 (0%)      |    17/50 (34%)     21/50 (42%)     13/50 (26%)     |
|ADJUSTED (b)           |     14.4%            0.0%            0.0%          |     46.7%           56.0%           38.1%          |
|TERMINAL (d)           |     2/24 (8%)       0/21 (0%)       0/16 (0%)      |    11/30 (37%)     16/32 (50%)     10/31 (32%)     |
|FIRST INCIDENCE (DAYS) |      653             ---             ---           |      680             443             695           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.030N*       P=0.092N        P=0.120N       |     P=0.216N        P=0.338         P=0.251N       |
|INCIDENTAL TUMOR       |     P=0.028N*       P=0.112N        P=0.098N       |     P=0.168N        P=0.186         P=0.200N       |
|LOGISTIC REGRESSION    |     P=0.024N*       P=0.085N        P=0.094N       |     P=0.198N        P=0.264         P=0.292N       |
|COCHRAN-ARMITAGE       |     P=0.015N*                                      |     P=0.230N                                       |
|FISHER EXACT           |                     P=0.059N        P=0.059N       |                     P=0.268         P=0.257N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       0/50 (0%)       0/50 (0%)      |    19/50 (38%)     21/50 (42%)     13/50 (26%)     |
|ADJUSTED (b)           |     14.4%            0.0%            0.0%          |     48.9%           56.0%           38.1%          |
|TERMINAL (d)           |     2/24 (8%)       0/21 (0%)       0/16 (0%)      |    11/30 (37%)     16/32 (50%)     10/31 (32%)     |
|FIRST INCIDENCE (DAYS) |      653             ---             ---           |      199             443             695           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.030N*       P=0.092N        P=0.120N       |     P=0.122N        P=0.492         P=0.147N       |
|INCIDENTAL TUMOR       |     P=0.028N*       P=0.112N        P=0.098N       |     P=0.101N        P=0.307         P=0.127N       |
|LOGISTIC REGRESSION    |     P=0.024N*       P=0.085N        P=0.094N       |     P=0.103N        P=0.438         P=0.122N       |
|COCHRAN-ARMITAGE       |     P=0.015N*                                      |     P=0.125N                                       |
|FISHER EXACT           |                     P=0.059N        P=0.059N       |                     P=0.419         P=0.142N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   7
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/22 (5%)       3/50 (6%)      |     0/49 (0%)       1/13 (8%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%           33.3%           18.8%          |      0.0%          100.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       1/3 (33%)       3/16 (19%)     |     0/30 (0%)       1/1 (100%)      0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         729 (T)       |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.114         P=0.262         P=0.170        |     P=0.687N        P=0.004 **        (e)          |
|INCIDENTAL TUMOR       |     P=0.114         P=0.262         P=0.170        |     P=0.687N        P=0.004 **        (e)          |
|LOGISTIC REGRESSION    |     P=0.114         P=0.262         P=0.170        |     P=0.687N        P=0.004 **        (e)          |
|COCHRAN-ARMITAGE       |     P=0.225                                        |     P=0.700N                                       |
|FISHER EXACT           |                     P=0.521         P=0.309        |                     P=0.210           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    23/50 (46%)     17/50 (34%)     14/49 (29%)     |    22/50 (44%)     26/50 (52%)     25/50 (50%)     |
|ADJUSTED (b)           |     60.3%           54.2%           56.3%          |     63.9%           64.8%           67.0%          |
|TERMINAL (d)           |    10/24 (42%)      8/21 (38%)      7/16 (44%)     |    18/30 (60%)     18/32 (56%)     19/31 (61%)     |
|FIRST INCIDENCE (DAYS) |      426             463             512           |      481             540             498           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.286N        P=0.366N        P=0.337N       |     P=0.360         P=0.362         P=0.395        |
|INCIDENTAL TUMOR       |     P=0.088N        P=0.265N        P=0.105N       |     P=0.393         P=0.341         P=0.429        |
|LOGISTIC REGRESSION    |     P=0.080N        P=0.223N        P=0.094N       |     P=0.347         P=0.262         P=0.387        |
|COCHRAN-ARMITAGE       |     P=0.044N*                                      |     P=0.308                                        |
|FISHER EXACT           |                     P=0.154N        P=0.056N       |                     P=0.274         P=0.344        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   8
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       1/49 (2%)      |     2/50 (4%)       0/50 (0%)       3/50 (6%)      |
|ADJUSTED (b)           |      3.3%            0.0%            2.8%          |      5.5%            0.0%            8.2%          |
|TERMINAL (d)           |     0/24 (0%)       0/21 (0%)       0/16 (0%)      |     1/30 (3%)       0/32 (0%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      681             ---             546           |      536             ---             669           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.610         P=0.536N        P=0.700        |     P=0.402         P=0.233N        P=0.513        |
|INCIDENTAL TUMOR       |     P=0.608N        P=0.607N        P=0.705N       |     P=0.428         P=0.160N        P=0.547        |
|LOGISTIC REGRESSION    |     P=0.665N        P=0.524N        P=0.750N       |     P=0.389         P=0.245N        P=0.500        |
|COCHRAN-ARMITAGE       |     P=0.665                                        |     P=0.390                                        |
|FISHER EXACT           |                     P=0.500N        P=0.747        |                     P=0.247N        P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    24/50 (48%)     17/50 (34%)     15/49 (31%)     |    24/50 (48%)     26/50 (52%)     28/50 (56%)     |
|ADJUSTED (b)           |     61.6%           54.2%           57.5%          |     67.7%           64.8%           71.3%          |
|TERMINAL (d)           |    10/24 (42%)      8/21 (38%)      7/16 (44%)     |    19/30 (63%)     18/32 (56%)     20/31 (65%)     |
|FIRST INCIDENCE (DAYS) |      426             463             512           |      481             540             498           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.301N        P=0.311N        P=0.360N       |     P=0.299         P=0.514         P=0.333        |
|INCIDENTAL TUMOR       |     P=0.084N        P=0.218N        P=0.097N       |     P=0.329         P=0.535         P=0.371        |
|LOGISTIC REGRESSION    |     P=0.081N        P=0.170N        P=0.094N       |     P=0.280         P=0.427         P=0.319        |
|COCHRAN-ARMITAGE       |     P=0.046N*                                      |     P=0.242                                        |
|FISHER EXACT           |                     P=0.111N        P=0.059N       |                     P=0.421         P=0.274        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE   9
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       0/19 (0%)       1/50 (2%)      |                                                    |
|ADJUSTED (b)           |      8.3%            0.0%            5.3%          |                                                    |
|TERMINAL (d)           |     2/24 (8%)       0/0             0/16 (0%)      |                                                    |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             725           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.495N          (e)           P=0.620N       |                                                    |
|INCIDENTAL TUMOR       |     P=0.487N          (e)           P=0.603N       |                                                    |
|LOGISTIC REGRESSION    |     P=0.484N          (e)           P=0.603N       |                                                    |
|COCHRAN-ARMITAGE       |     P=0.369N                                       |                                                    |
|FISHER EXACT           |                     P=0.516N        P=0.492N       |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       4/50 (8%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      6.2%            0.0%           18.3%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       0/21 (0%)       2/16 (13%)     |     0/30 (0%)       0/32 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      522             ---             561           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.140         P=0.279N        P=0.207        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.197         P=0.226N        P=0.295        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.203         P=0.224N        P=0.315        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.222                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.247N        P=0.339        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  10
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%            4.8%            8.8%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       1/21 (5%)       1/16 (6%)      |     0/30 (0%)       0/32 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         541           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.276         P=0.733         P=0.390        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.332         P=0.733         P=0.476        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.332         P=0.733         P=0.469        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.378                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.753N        P=0.500        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      4.2%            8.7%            6.3%          |      0.0%            0.0%            3.2%          |
|TERMINAL (d)           |     1/24 (4%)       1/21 (5%)       1/16 (6%)      |     0/30 (0%)       0/32 (0%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         686             729 (T)       |      ---             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.503         P=0.451         P=0.670        |     P=0.273           (e)           P=0.507        |
|INCIDENTAL TUMOR       |     P=0.518         P=0.408         P=0.670        |     P=0.273           (e)           P=0.507        |
|LOGISTIC REGRESSION    |     P=0.535         P=0.435         P=0.670        |     P=0.273           (e)           P=0.507        |
|COCHRAN-ARMITAGE       |     P=0.622N                                       |     P=0.269                                        |
|FISHER EXACT           |                     P=0.500         P=0.753N       |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  11
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       3/50 (6%)       6/50 (12%)     |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |     14.4%           13.3%           26.2%          |      0.0%            0.0%            3.2%          |
|TERMINAL (d)           |     3/24 (13%)      2/21 (10%)      3/16 (19%)     |     0/30 (0%)       0/32 (0%)       1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      522             686             541           |      ---             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.148         P=0.581N        P=0.191        |     P=0.273           (e)           P=0.507        |
|INCIDENTAL TUMOR       |     P=0.220         P=0.574N        P=0.297        |     P=0.273           (e)           P=0.507        |
|LOGISTIC REGRESSION    |     P=0.230         P=0.581N        P=0.316        |     P=0.273           (e)           P=0.507        |
|COCHRAN-ARMITAGE       |     P=0.297                                        |     P=0.269                                        |
|FISHER EXACT           |                     P=0.500N        P=0.370        |                       (e)           P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/50 (2%)       1/50 (2%)      |     3/50 (6%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%            4.8%            5.9%          |      8.8%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       1/21 (5%)       0/16 (0%)      |     2/30 (7%)       0/32 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         728           |      536             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.536         P=0.733         P=0.675        |     P=0.036N*       P=0.115N        P=0.118N       |
|INCIDENTAL TUMOR       |     P=0.557         P=0.733         P=0.706        |     P=0.027N*       P=0.078N        P=0.102N       |
|LOGISTIC REGRESSION    |     P=0.558         P=0.733         P=0.697        |     P=0.037N*       P=0.121N        P=0.121N       |
|COCHRAN-ARMITAGE       |     P=0.640                                        |     P=0.037N*                                      |
|FISHER EXACT           |                     P=0.753N        P=0.753N       |                     P=0.121N        P=0.121N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  12
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       1/50 (2%)       2/50 (4%)      |     4/50 (8%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |     10.5%            4.8%           11.8%          |     11.5%            5.5%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       1/21 (5%)       1/16 (6%)      |     2/30 (7%)       1/32 (3%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      549             729 (T)         728           |      536             617             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.543N        P=0.356N        P=0.657N       |     P=0.037N*       P=0.328N        P=0.064N       |
|INCIDENTAL TUMOR       |     P=0.503N        P=0.318N        P=0.605N       |     P=0.029N*       P=0.253N        P=0.053N       |
|LOGISTIC REGRESSION    |     P=0.482N        P=0.350N        P=0.583N       |     P=0.036N*       P=0.334N        P=0.062N       |
|COCHRAN-ARMITAGE       |     P=0.399N                                       |     P=0.037N*                                      |
|FISHER EXACT           |                     P=0.309N        P=0.500N       |                     P=0.339N        P=0.059N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     3/50 (6%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      6.4%            4.8%            5.9%          |      8.8%            2.4%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       1/21 (5%)       0/16 (0%)      |     2/30 (7%)       0/32 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      549             729 (T)         728           |      536             617             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.486N        P=0.548N        P=0.609N       |     P=0.059N        P=0.299N        P=0.118N       |
|INCIDENTAL TUMOR       |     P=0.440N        P=0.502N        P=0.541N       |     P=0.042N*       P=0.170N        P=0.102N       |
|LOGISTIC REGRESSION    |     P=0.428N        P=0.532N        P=0.534N       |     P=0.063N        P=0.310N        P=0.121N       |
|COCHRAN-ARMITAGE       |     P=0.378N                                       |     P=0.060N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.309N        P=0.121N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  13
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/29 (7%)       1/50 (2%)      |     0/50 (0%)       0/20 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      6.2%           19.5%            6.3%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       1/6 (17%)       1/16 (6%)      |     0/30 (0%)       0/3 (0%)        0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      440             639             729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.526N        P=0.422         P=0.596N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.453N        P=0.498         P=0.524N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.435N        P=0.434         P=0.489N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.398N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.468         P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    42/50 (84%)     42/50 (84%)     46/50 (92%)     |                                                    |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |                                                    |
|TERMINAL (d)           |    24/24 (100%)    21/21 (100%)    16/16 (100%)    |                                                    |
|FIRST INCIDENCE (DAYS) |      481             450             433           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.008 **      P=0.193         P=0.010 **     |                                                    |
|INCIDENTAL TUMOR       |     P=0.004 **      P=0.091         P=0.008 **     |                                                    |
|LOGISTIC REGRESSION    |     P=0.010 **      P=0.083         P=0.023 *      |                                                    |
|COCHRAN-ARMITAGE       |     P=0.152                                        |                                                    |
|FISHER EXACT           |                     P=0.607N        P=0.178        |                                                    |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  14
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       4/20 (20%)      3/50 (6%)      |     7/50 (14%)      0/12 (0%)       7/50 (14%)     |
|ADJUSTED (b)           |     13.8%          100.0%           13.3%          |     21.8%            0.0%           22.6%          |
|TERMINAL (d)           |     2/24 (8%)       1/1 (100%)      1/16 (6%)      |     6/30 (20%)      0/0             7/31 (23%)     |
|FIRST INCIDENCE (DAYS) |      647             561             610           |      481             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.520         P=0.170         P=0.632        |     P=0.533N        P=0.500N        P=0.590N       |
|INCIDENTAL TUMOR       |     P=0.531N        P=0.014 *       P=0.603N       |     P=0.525N        P=0.362N        P=0.576N       |
|LOGISTIC REGRESSION    |     P=0.512N        P=0.008 **      P=0.584N       |     P=0.545N        P=0.367N        P=0.597N       |
|COCHRAN-ARMITAGE       |     P=0.431N                                       |     P=0.560                                        |
|FISHER EXACT           |                     P=0.156         P=0.500N       |                     P=0.203N        P=0.613N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/20 (0%)       2/50 (4%)      |     2/50 (4%)       1/12 (8%)       3/50 (6%)      |
|ADJUSTED (b)           |      8.3%            0.0%            6.6%          |      5.9%            0.0%            7.9%          |
|TERMINAL (d)           |     2/24 (8%)       0/1 (0%)        0/16 (0%)      |     1/30 (3%)       0/0             1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             468           |      682             568             645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.500         P=0.939N        P=0.588        |     P=0.420         P=0.760         P=0.510        |
|INCIDENTAL TUMOR       |     P=0.558         P=0.939N        P=0.670        |     P=0.441         P=0.682         P=0.530        |
|LOGISTIC REGRESSION    |     P=0.574         P=0.939N        P=0.685        |     P=0.420         P=0.489         P=0.510        |
|COCHRAN-ARMITAGE       |     P=0.610                                        |     P=0.412                                        |
|FISHER EXACT           |                     P=0.507N        P=0.691N       |                     P=0.482         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  15
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)      4/20 (20%)      5/50 (10%)     |     9/50 (18%)      1/12 (8%)      10/50 (20%)     |
|ADJUSTED (b)           |     21.6%          100.0%           19.1%          |     27.1%            0.0%           29.4%          |
|TERMINAL (d)           |     4/24 (17%)      1/1 (100%)      1/16 (6%)      |     7/30 (23%)      0/0             8/31 (26%)     |
|FIRST INCIDENCE (DAYS) |      647             561             468           |      481             568             645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.457         P=0.192         P=0.538        |     P=0.479         P=0.500N        P=0.530        |
|INCIDENTAL TUMOR       |     P=0.554N        P=0.022 *       P=0.602N       |     P=0.495         P=0.572N        P=0.553        |
|LOGISTIC REGRESSION    |     P=0.532N        P=0.012 *       P=0.577N       |     P=0.473         P=0.629N        P=0.525        |
|COCHRAN-ARMITAGE       |     P=0.440N                                       |     P=0.448                                        |
|FISHER EXACT           |                     P=0.304         P=0.500N       |                     P=0.375N        P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/20 (0%)       0/50 (0%)      |     0/50 (0%)       0/12 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      0.0%            0.0%            6.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/1 (0%)        0/16 (0%)      |     0/30 (0%)       0/0             1/31 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      ---             ---             695           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.124           (e)           P=0.240        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.154           (e)           P=0.253        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.141           (e)           P=0.242        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.129                                        |
|FISHER EXACT           |                       (e)             (e)          |                       (e)           P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  16
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/20 (0%)       0/50 (0%)      |     0/50 (0%)       0/12 (0%)       3/50 (6%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      0.0%            0.0%            9.1%          |
|TERMINAL (d)           |     0/24 (0%)       0/1 (0%)        0/16 (0%)      |     0/30 (0%)       0/0             2/31 (6%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      ---             ---             695           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.064           (e)           P=0.125        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.080           (e)           P=0.132        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.070           (e)           P=0.122        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.061                                        |
|FISHER EXACT           |                       (e)             (e)          |                       (e)           P=0.121        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    12/50 (24%)      4/50 (8%)       9/50 (18%)     |
|ADJUSTED (b)           |                                                    |     34.4%           10.9%           26.2%          |
|TERMINAL (d)           |                                                    |     8/30 (27%)      2/32 (6%)       7/31 (23%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      680             617             411           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.242N        P=0.029N*       P=0.298N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.216N        P=0.025N*       P=0.261N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.232N        P=0.027N*       P=0.287N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.251N                                       |
|FISHER EXACT           |                                                    |                     P=0.027N*       P=0.312N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  17
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)      4/50 (8%)       5/50 (10%)     |    13/50 (26%)      7/50 (14%)     11/50 (22%)     |
|ADJUSTED (b)           |     23.1%           14.8%           18.5%          |     37.5%           18.1%           26.2%          |
|TERMINAL (d)           |     4/24 (17%)      2/21 (10%)      0/16 (0%)      |     9/30 (30%)      1/32 (3%)       3/31 (10%)     |
|FIRST INCIDENCE (DAYS) |      522             463             595           |      246             620             526           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.504N        P=0.357N        P=0.588N       |     P=0.344N        P=0.106N        P=0.383N       |
|INCIDENTAL TUMOR       |     P=0.364N        P=0.322N        P=0.435N       |     P=0.339N        P=0.178N        P=0.399N       |
|LOGISTIC REGRESSION    |     P=0.359N        P=0.297N        P=0.433N       |     P=0.351N        P=0.101N        P=0.404N       |
|COCHRAN-ARMITAGE       |     P=0.314N                                       |     P=0.356N                                       |
|FISHER EXACT           |                     P=0.262N        P=0.380N       |                     P=0.105N        P=0.408N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       3/50 (6%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      8.3%           10.4%            0.0%          |      0.0%            0.0%            2.2%          |
|TERMINAL (d)           |     2/24 (8%)       1/21 (5%)       0/16 (0%)      |     0/30 (0%)       0/32 (0%)       0/31 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         561             ---           |      ---             ---             570           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.298N        P=0.434         P=0.330N       |     P=0.278           (e)           P=0.509        |
|INCIDENTAL TUMOR       |     P=0.248N        P=0.509         P=0.330N       |     P=0.227           (e)           P=0.500        |
|LOGISTIC REGRESSION    |     P=0.238N        P=0.449         P=0.330N       |     P=0.232           (e)           P=0.460        |
|COCHRAN-ARMITAGE       |     P=0.202N                                       |     P=0.269                                        |
|FISHER EXACT           |                     P=0.500         P=0.247N       |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  18
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    47/50 (94%)     45/50 (90%)     48/50 (96%)     |    32/50 (64%)     38/50 (76%)     39/50 (78%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     81.8%           84.4%           95.0%          |
|TERMINAL (d)           |    24/24 (100%)    21/21 (100%)    16/16 (100%)    |    23/30 (77%)     25/32 (78%)     29/31 (94%)     |
|FIRST INCIDENCE (DAYS) |      426             450             433           |      481             443             411           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.028 *       P=0.282         P=0.030 *      |     P=0.154         P=0.268         P=0.162        |
|INCIDENTAL TUMOR       |     P=0.014 *       P=0.199         P=0.032 *      |     P=0.135         P=0.182         P=0.158        |
|LOGISTIC REGRESSION    |     P=0.087         P=0.272         P=0.160        |     P=0.092         P=0.138         P=0.111        |
|COCHRAN-ARMITAGE       |     P=0.421                                        |     P=0.072                                        |
|FISHER EXACT           |                     P=0.357N        P=0.500        |                     P=0.138         P=0.093        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    24/50 (48%)     16/50 (32%)     19/50 (38%)     |    23/50 (46%)     13/50 (26%)     19/50 (38%)     |
|ADJUSTED (b)           |     65.7%           49.0%           57.0%          |     59.0%           31.1%           41.8%          |
|TERMINAL (d)           |    13/24 (54%)      7/21 (33%)      4/16 (25%)     |    15/30 (50%)      4/32 (13%)      6/31 (19%)     |
|FIRST INCIDENCE (DAYS) |      440             360             327           |      193             540             379           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.497         P=0.234N        P=0.490        |     P=0.239N        P=0.039N*       P=0.269N       |
|INCIDENTAL TUMOR       |     P=0.214N        P=0.082N        P=0.230N       |     P=0.246N        P=0.035N*       P=0.296N       |
|LOGISTIC REGRESSION    |     P=0.209N        P=0.097N        P=0.236N       |     P=0.268N        P=0.034N*       P=0.312N       |
|COCHRAN-ARMITAGE       |     P=0.178N                                       |     P=0.234N                                       |
|FISHER EXACT           |                     P=0.076N        P=0.210N       |                     P=0.030N*       P=0.272N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05043 TEST: 01                                                 PAGE  19
                    STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 2,4-DIAMINOPHENOL DIHYDROCHLORIDE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         .0125 G/        .025G/KG      |      VEHICLE         .0125 G/        .025G/KG      |
|                       |      72 VM           KG 72LM         72HM          |      72VF            KG 72LF         72HF          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    49/50 (98%)     46/50 (92%)     49/50 (98%)     |    41/50 (82%)     41/50 (82%)     47/50 (94%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     89.0%           87.2%           95.9%          |
|TERMINAL (d)           |    24/24 (100%)    21/21 (100%)    16/16 (100%)    |    25/30 (83%)     26/32 (81%)     29/31 (94%)     |
|FIRST INCIDENCE (DAYS) |      426             360             327           |      193             443             379           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.041 *       P=0.330         P=0.044 *      |     P=0.244         P=0.459N        P=0.270        |
|INCIDENTAL TUMOR       |     P=0.162         P=0.710         P=0.377        |     P=0.098         P=0.570N        P=0.105        |
|LOGISTIC REGRESSION    |     P=0.331         P=0.741         P=0.520        |     P=0.074         P=0.569N        P=0.073        |
|COCHRAN-ARMITAGE       |     P=0.601                                        |     P=0.056                                        |
|FISHER EXACT           |                     P=0.181N        P=0.753N       |                     P=0.602N        P=0.061        |
|=================================================================================================================================|
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
 
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).

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