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TDMS Study 05166-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: HLA, VA                                      3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94       
EXPERIMENT: 05166 TEST: 01                                                                                     TIME: 01:07:05       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99990        
PATHOLOGIST: G. PARKER                       S. EUSTIS                                                         CAS: 612-82-8        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: HLA, VA                                      3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94      
EXPERIMENT: 05166 TEST: 01                                                                                     TIME: 01:07:05      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99990       
PATHOLOGIST: G. PARKER                       S. EUSTIS                                                         CAS: 612-82-8       
 
 
 
 
 
                                                    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: HLA, VA                                      3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94       
EXPERIMENT: 05166 TEST: 01                                                                                     TIME: 01:07:05       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99990        
PATHOLOGIST: G. PARKER                       S. EUSTIS                                                         CAS: 612-82-8        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                             IN THE ANALYSIS OF THE STUDY OF 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                             Brain                         Oligodendroglioma, Glioma, or Astrocytoma
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             Intestine Large               Carcinoma
                                                           Carcinoma or Adenoma
                                                           Polyp Adenomatous
                             Intestine Small               Carcinoma
                                                           Carcinoma or Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatoblastoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)
                                                           Papilloma Squamous or Papilloma
                                                           Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma
                             Pharynx                       Squamous Cell Papilloma
                             Skin                          Basal Cell Adenoma
                                                           Basal Cell Carcinoma
                                                           Keratoacanthoma
                                                           Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma
                                                           Squamous Cell Papilloma
                                                           Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma
                                                           Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,
                                                            Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma
                             Skin: Sebaceous Gland         Carcinoma, Basal Cell Carcinoma or Adenoma
                             Skin: Subcutaneous Tissue     Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                             Testes                        Adenoma
                             Thyroid Gland: C-Cell         Adenoma
                             Tongue                        Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma or Papilloma Squamous
                             Zymbal's Gland                Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             All Organs                    Mesothelioma Benign, Malignant, NOS
                                                           Benign Tumors
                                                           Malignant Tumors
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: HLA, VA                                      3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94       
EXPERIMENT: 05166 TEST: 01                                                                                     TIME: 01:07:05       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99990        
PATHOLOGIST: G. PARKER                       S. EUSTIS                                                         CAS: 612-82-8        
 
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             Intestine Large               Polyp Adenomatous
                             Intestine Small               Carcinoma
                                                           Carcinoma or Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatoblastoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Mammary Gland                 Carcinoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)
                                                           Papilloma Squamous or Papilloma
                                                           Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma
                             Pharynx                       Squamous Cell Carcinoma
                                                           Squamous Cell Papilloma
                             Skin                          Basal Cell Adenoma
                                                           Basal Cell Carcinoma
                                                           Keratoacanthoma
                                                           Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma
                                                           Squamous Cell Papilloma
                                                           Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma
                                                           Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,
                                                            Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma
                             Skin: Sebaceous Gland         Carcinoma, Basal Cell Carcinoma or Adenoma
                             Tongue                        Squamous Cell Carcinoma or Papilloma Squamous
                                                           Squamous Cell Papilloma
                             Uterus                        Polyp Stromal
                                                           Sarcoma Stromal or Polyp Stromal
                             Zymbal's Gland                Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   1
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/45 (4%)    1/75 (1%)    3/59 (5%)  |  0/60 (0%)    0/45 (0%)    0/74 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         4.9%         2.0%        56.7%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/60 (0%)    2/41 (5%)    1/50 (2%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          419 (T)      419 (T)      349       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.160      P=0.464      P<0.001 ** |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.129      P=0.160      P=0.464        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.029 *    P=0.160      P=0.464      P=0.024 *  |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.129                                           |    (e)                                             |
|FISHER EXACT           |               P=0.181      P=0.556      P=0.119    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    1/75 (1%)    1/60 (2%)  |  0/60 (0%)    1/45 (2%)    2/75 (3%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.0%         6.7%      |   0.0%         2.6%         6.1%         3.8%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    1/50 (2%)    0/0        |  0/59 (0%)    1/39 (3%)    1/32 (3%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      350       |   ---          421 (T)      419          383       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.022 *      (e)        P=0.464      P=0.227    |  P=0.075      P=0.417      P=0.122      P=0.333    |
|INCIDENTAL TUMOR       |  P=0.368        (e)        P=0.464        (e)      |  P=0.429      P=0.417      P=0.357      P=0.983    |
|LOGISTIC REGRESSION    |  P=0.185        (e)        P=0.464      P=0.656    |  P=0.190      P=0.417      P=0.136      P=0.518    |
|COCHRAN-ARMITAGE       |  P=0.262                                           |  P=0.428                                           |
|FISHER EXACT           |                 (e)        P=0.556      P=0.500    |               P=0.429      P=0.307      P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   2
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    4/45 (9%)    4/75 (5%)    8/60 (13%) |  0/60 (0%)    9/45 (20%)  32/75 (43%)  17/59 (29%) |
|ADJUSTED (b)           |   3.3%         9.8%         8.0%        38.3%      |   0.0%        20.9%        61.1%        66.9%      |
|TERMINAL (d)           |  2/60 (3%)    4/41 (10%)   4/50 (8%)    0/0        |  0/59 (0%)    5/39 (13%)  14/32 (44%)   5/10 (50%) |
|FIRST INCIDENCE (DAYS) |   419 (T)      419 (T)      419 (T)      280       |   ---          391          229          296       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.182      P=0.258      P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.044 *    P=0.182      P=0.258        (e)      |  P=0.019 *    P=0.003 **   P<0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.016 *    P=0.182      P=0.258      P=0.036 *  |  P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.043 *                                         |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.214      P=0.451      P=0.047 *  |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    2/75 (3%)    1/60 (2%)  |  0/60 (0%)    5/45 (11%)  11/75 (15%)  18/59 (31%) |
|ADJUSTED (b)           |   0.0%         0.0%         4.0%         2.6%      |   0.0%        12.8%        22.4%        65.1%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    2/50 (4%)    0/0        |  0/59 (0%)    5/39 (13%)   3/32 (9%)    3/10 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      308       |   ---          421 (T)      315          254       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.025 *      (e)        P=0.200      P=0.409    |  P<0.001 **   P=0.010 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.160        (e)        P=0.200        (e)      |  P<0.001 **   P=0.010 **   P=0.033 *    P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.231        (e)        P=0.200      P=0.902    |  P<0.001 **   P=0.010 **   P=0.004 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.283                                           |  P<0.001 **                                        |
|FISHER EXACT           |                 (e)        P=0.307      P=0.500    |               P=0.013 *    P=0.001 **   P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   3
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    4/45 (9%)    6/75 (8%)    9/60 (15%) |  0/60 (0%)   14/45 (31%)  42/75 (56%)  32/59 (54%) |
|ADJUSTED (b)           |   3.3%         9.8%        12.0%        39.9%      |   0.0%        32.6%        70.4%        89.2%      |
|TERMINAL (d)           |  2/60 (3%)    4/41 (10%)   6/50 (12%)   0/0        |  0/59 (0%)   10/39 (26%)  16/32 (50%)   7/10 (70%) |
|FIRST INCIDENCE (DAYS) |   419 (T)      419 (T)      419 (T)      280       |   ---          391          229          254       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.182      P=0.086      P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.012 *    P=0.182      P=0.086        (e)      |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.006 **   P=0.182      P=0.086      P=0.030 *  |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.023 *                                         |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.214      P=0.222      P=0.027 *  |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    7/60 (12%) |  0/60 (0%)    0/45 (0%)    1/75 (1%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%        33.9%      |   0.0%         0.0%         2.1%         6.3%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          309       |   ---          ---          390          405       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)          (e)        P<0.001 ** |  P=0.083        (e)        P=0.451      P=0.242    |
|INCIDENTAL TUMOR       |  P=0.189        (e)          (e)          (e)      |  P=0.587        (e)        P=0.989      P=0.983    |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)          (e)        P=0.003 ** |  P=0.189        (e)        P=0.584      P=0.372    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.262                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.006 ** |                 (e)        P=0.556      P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   4
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large: Colon                                                                                                           |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    6/60 (10%) |  0/60 (0%)    0/45 (0%)    0/75 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%        31.3%      |   0.0%         0.0%         0.0%         6.3%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          309       |   ---          ---          ---          405       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)          (e)        P<0.001 ** |  P=0.069        (e)          (e)        P=0.242    |
|INCIDENTAL TUMOR       |  P=0.230        (e)          (e)          (e)      |  P=0.391        (e)          (e)        P=0.983    |
|LOGISTIC REGRESSION    |  P=0.001 **     (e)          (e)        P=0.007 ** |  P=0.118        (e)          (e)        P=0.372    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.209                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.014 *  |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large: Colon                                                                                                           |
|     Polyp Adenomatous                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    5/75 (7%)    5/60 (8%)  |  0/60 (0%)    1/45 (2%)    4/75 (5%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         9.5%        24.9%      |   0.0%         2.6%        10.7%        12.7%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    4/50 (8%)    0/0        |  0/59 (0%)    1/39 (3%)    3/32 (9%)    1/10 (10%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          384          308       |   ---          421 (T)      310          355       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.024 *    P<0.001 ** |  P=0.009 **   P=0.417      P=0.023 *    P=0.046 *  |
|INCIDENTAL TUMOR       |  P=0.041 *      (e)        P=0.043 *      (e)      |  P=0.067      P=0.417      P=0.039 *    P=0.157    |
|LOGISTIC REGRESSION    |  P=0.005 **     (e)        P=0.039 *    P=0.046 *  |  P=0.134      P=0.417      P=0.091      P=0.171    |
|COCHRAN-ARMITAGE       |  P=0.009 **                                        |  P=0.214                                           |
|FISHER EXACT           |                 (e)        P=0.050 *    P=0.029 *  |               P=0.429      P=0.092      P=0.248    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   5
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large: Rectum                                                                                                          |
|     Polyp Adenomatous                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    3/60 (5%)  |  0/60 (0%)    0/45 (0%)    2/75 (3%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%        35.8%      |   0.0%         0.0%         4.6%        12.5%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    0/39 (0%)    1/32 (3%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          338       |   ---          ---          338          405       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)          (e)        P<0.001 ** |  P=0.008 **     (e)        P=0.180      P=0.031 *  |
|INCIDENTAL TUMOR       |  P=0.060        (e)          (e)          (e)      |  P=0.266        (e)        P=0.378      P=0.916    |
|LOGISTIC REGRESSION    |  P=0.014 *      (e)          (e)        P=0.026 *  |  P=0.063        (e)        P=0.344      P=0.084    |
|COCHRAN-ARMITAGE       |  P=0.012 *                                         |  P=0.102                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.122    |                 (e)        P=0.307      P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    3/75 (4%)    8/60 (13%) |  0/60 (0%)    0/45 (0%)    2/75 (3%)    5/60 (8%)  |
|ADJUSTED (b)           |   0.0%         0.0%         6.0%        61.2%      |   0.0%         0.0%         3.1%        24.4%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    3/50 (6%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      211       |   ---          ---          309          251       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.092      P<0.001 ** |  P<0.001 **     (e)        P=0.252      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.010 **     (e)        P=0.092        (e)      |  P=0.160        (e)          (e)        P=0.785    |
|LOGISTIC REGRESSION    |  P=0.003 **     (e)        P=0.092      P=0.096    |  P=0.009 **     (e)        P=0.487      P=0.026 *  |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.003 **                                        |
|FISHER EXACT           |                 (e)        P=0.168      P=0.003 ** |                 (e)        P=0.307      P=0.029 *  |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   6
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Duodenum                                                                                                        |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    2/75 (3%)    0/60 (0%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         4.0%         0.0%      |   0.0%         0.0%         0.0%         1.8%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    2/50 (4%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      ---       |   ---          ---          ---          251       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.187        (e)        P=0.200        (e)      |  P=0.203        (e)          (e)        P=0.490    |
|INCIDENTAL TUMOR       |  P=0.187        (e)        P=0.200        (e)      |  P=0.561        (e)          (e)        P=1.000    |
|LOGISTIC REGRESSION    |  P=0.187        (e)        P=0.200        (e)      |  P=0.445        (e)          (e)        P=0.973    |
|COCHRAN-ARMITAGE       |  P=0.649                                           |  P=0.209                                           |
|FISHER EXACT           |                 (e)        P=0.307        (e)      |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    1/75 (1%)    7/60 (12%) |  0/60 (0%)    0/45 (0%)    2/75 (3%)    3/60 (5%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.0%        22.3%      |   0.0%         0.0%         3.1%        16.7%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    1/50 (2%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      211       |   ---          ---          309          391       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.464      P<0.001 ** |  P=0.002 **     (e)        P=0.252      P=0.006 ** |
|INCIDENTAL TUMOR       |  P=0.105        (e)        P=0.464        (e)      |  P=0.394        (e)          (e)        P=0.846    |
|LOGISTIC REGRESSION    |  P=0.006 **     (e)        P=0.464      P=0.247    |  P=0.042 *      (e)        P=0.487      P=0.029 *  |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.034 *                                         |
|FISHER EXACT           |                 (e)        P=0.556      P=0.006 ** |                 (e)        P=0.307      P=0.122    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   7
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)   29/75 (39%)  26/60 (43%) |  0/60 (0%)    0/45 (0%)    7/74 (9%)    3/60 (5%)  |
|ADJUSTED (b)           |   0.0%         0.0%        51.7%       100.0%      |   0.0%         0.0%        20.3%        13.0%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)   23/50 (46%)   0/0        |  0/59 (0%)    0/39 (0%)    6/32 (19%)   0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          393          280       |   ---          ---          378          343       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P<0.001 **     (e)        P<0.001 **   P=0.021 *  |
|INCIDENTAL TUMOR       |  P<0.001 **     (e)        P<0.001 **     (e)      |  P=0.024 *      (e)        P=0.001 **   P=0.983    |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P=0.015 *      (e)        P=0.003 **   P=0.133    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.074                                           |
|FISHER EXACT           |                 (e)        P<0.001 **   P<0.001 ** |                 (e)        P=0.014 *    P=0.122    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)   12/75 (16%)  12/60 (20%) |  0/60 (0%)    0/45 (0%)    1/74 (1%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%        23.3%        75.5%      |   0.0%         0.0%         3.1%         6.3%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)   11/50 (22%)   0/0        |  0/59 (0%)    0/39 (0%)    1/32 (3%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          379          238       |   ---          ---          421 (T)      405       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P=0.048 *      (e)        P=0.378      P=0.242    |
|INCIDENTAL TUMOR       |  P<0.001 **     (e)        P<0.001 **     (e)      |  P=0.225        (e)        P=0.378      P=0.983    |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P=0.094        (e)        P=0.378      P=0.372    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.262                                           |
|FISHER EXACT           |                 (e)        P<0.001 **   P<0.001 ** |                 (e)        P=0.552      P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   8
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)   12/75 (16%)  12/60 (20%) |  0/60 (0%)    0/45 (0%)    1/74 (1%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%        23.3%        75.5%      |   0.0%         0.0%         3.1%         6.3%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)   11/50 (22%)   0/0        |  0/59 (0%)    0/39 (0%)    1/32 (3%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          379          238       |   ---          ---          421 (T)      405       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P=0.048 *      (e)        P=0.378      P=0.242    |
|INCIDENTAL TUMOR       |  P<0.001 **     (e)        P<0.001 **     (e)      |  P=0.225        (e)        P=0.378      P=0.983    |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P=0.094        (e)        P=0.378      P=0.372    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.262                                           |
|FISHER EXACT           |                 (e)        P<0.001 **   P<0.001 ** |                 (e)        P=0.552      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)   35/75 (47%)  33/60 (55%) |  0/60 (0%)    0/45 (0%)    7/74 (9%)    4/60 (7%)  |
|ADJUSTED (b)           |   0.0%         0.0%        61.3%       100.0%      |   0.0%         0.0%        20.3%        18.4%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)   28/50 (56%)   0/0        |  0/59 (0%)    0/39 (0%)    6/32 (19%)   0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          379          238       |   ---          ---          378          343       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P<0.001 **     (e)        P<0.001 **   P=0.004 ** |
|INCIDENTAL TUMOR       |  P<0.001 **     (e)        P<0.001 **     (e)      |  P=0.012 *      (e)        P=0.001 **   P=0.916    |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P=0.003 **     (e)        P=0.003 **   P=0.042 *  |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.032 *                                         |
|FISHER EXACT           |                 (e)        P<0.001 **   P<0.001 ** |                 (e)        P=0.014 *    P=0.059    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE   9
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)   35/75 (47%)  33/60 (55%) |  0/60 (0%)    0/45 (0%)    7/74 (9%)    4/60 (7%)  |
|ADJUSTED (b)           |   0.0%         0.0%        61.3%       100.0%      |   0.0%         0.0%        20.3%        18.4%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)   28/50 (56%)   0/0        |  0/59 (0%)    0/39 (0%)    6/32 (19%)   0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          379          238       |   ---          ---          378          343       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P<0.001 **     (e)        P<0.001 **   P=0.004 ** |
|INCIDENTAL TUMOR       |  P<0.001 **     (e)        P<0.001 **     (e)      |  P=0.012 *      (e)        P=0.001 **   P=0.916    |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)        P<0.001 **   P<0.001 ** |  P=0.003 **     (e)        P=0.003 **   P=0.042 *  |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.032 *                                         |
|FISHER EXACT           |                 (e)        P<0.001 **   P<0.001 ** |                 (e)        P=0.014 *    P=0.059    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/45 (0%)    7/75 (9%)    6/60 (10%) |  1/60 (2%)    1/45 (2%)    3/74 (4%)    3/60 (5%)  |
|ADJUSTED (b)           |   1.7%         0.0%        13.7%       100.0%      |   1.7%         2.6%         7.7%        16.3%      |
|TERMINAL (d)           |  1/60 (2%)    0/41 (0%)    6/50 (12%)   0/0        |  1/59 (2%)    1/39 (3%)    2/32 (6%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   419 (T)      ---          406          226       |   421 (T)      421 (T)      338          370       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.576N     P=0.019 *    P<0.001 ** |  P=0.006 **   P=0.666      P=0.165      P=0.023 *  |
|INCIDENTAL TUMOR       |  P=0.003 **   P=0.576N     P=0.035 *      (e)      |  P=0.202      P=0.666      P=0.293      P=0.842N   |
|LOGISTIC REGRESSION    |  P=0.025 *    P=0.576N     P=0.026 *    P=0.472    |  P=0.086      P=0.666      P=0.369      P=0.130    |
|COCHRAN-ARMITAGE       |  P=0.015 *                                         |  P=0.201                                           |
|FISHER EXACT           |               P=0.571N     P=0.061      P=0.057    |               P=0.676      P=0.393      P=0.309    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  10
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/45 (0%)    8/75 (11%)   6/60 (10%) |  1/60 (2%)    1/45 (2%)    3/74 (4%)    4/60 (7%)  |
|ADJUSTED (b)           |   1.7%         0.0%        15.6%       100.0%      |   1.7%         2.6%         7.7%        19.6%      |
|TERMINAL (d)           |  1/60 (2%)    0/41 (0%)    7/50 (14%)   0/0        |  1/59 (2%)    1/39 (3%)    2/32 (6%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   419 (T)      ---          406          226       |   421 (T)      421 (T)      338          370       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.576N     P=0.010 **   P<0.001 ** |  P=0.001 **   P=0.666      P=0.165      P=0.006 ** |
|INCIDENTAL TUMOR       |  P=0.001 **   P=0.576N     P=0.018 *      (e)      |  P=0.115      P=0.666      P=0.293      P=0.806    |
|LOGISTIC REGRESSION    |  P=0.006 **   P=0.576N     P=0.013 *    P=0.472    |  P=0.032 *    P=0.666      P=0.369      P=0.060    |
|COCHRAN-ARMITAGE       |  P=0.017 *                                         |  P=0.095                                           |
|FISHER EXACT           |               P=0.571N     P=0.036 *    P=0.057    |               P=0.676      P=0.393      P=0.182    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |  0/60 (0%)    1/45 (2%)    3/75 (4%)    6/60 (10%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         2.6%         6.5%        36.6%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    1/39 (3%)    1/32 (3%)    3/10 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          421 (T)      363          285       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.417      P=0.084      P<0.001 ** |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.001 **   P=0.417      P=0.357      P<0.001 ** |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.002 **   P=0.417      P=0.189      P=0.004 ** |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.005 **                                        |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.429      P=0.168      P=0.014 *  |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  11
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |  2/60 (3%)    1/45 (2%)    4/75 (5%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   3.4%         2.6%        11.7%         0.0%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  2/59 (3%)    1/39 (3%)    3/32 (9%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   421 (T)      421 (T)      406          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.426      P=0.642N     P=0.122      P=0.665N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.633      P=0.642N     P=0.230      P=0.665N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.549      P=0.642N     P=0.182      P=0.665N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.235N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.607N     P=0.451      P=0.248N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |  2/60 (3%)    2/45 (4%)    7/75 (9%)    6/60 (10%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   3.4%         5.1%        17.7%        36.6%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  2/59 (3%)    2/39 (5%)    4/32 (13%)   3/10 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   421 (T)      421 (T)      363          285       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.538      P=0.017 *    P<0.001 ** |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.009 **   P=0.538      P=0.104      P=0.011 *  |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.013 *    P=0.538      P=0.081      P=0.040 *  |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.084                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.576      P=0.149      P=0.136    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  12
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    3/75 (4%)    2/60 (3%)  |  0/60 (0%)    3/45 (7%)    7/75 (9%)    9/60 (15%) |
|ADJUSTED (b)           |   0.0%         0.0%         6.0%        35.4%      |   0.0%         7.7%        16.5%        43.7%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    3/50 (6%)    0/0        |  0/59 (0%)    3/39 (8%)    3/32 (9%)    3/10 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      324       |   ---          421 (T)      363          229       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.092      P=0.017 *  |  P<0.001 **   P=0.060      P=0.002 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.018 *      (e)        P=0.092        (e)      |  P=0.001 **   P=0.060      P=0.038 *    P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.019 *      (e)        P=0.092      P=0.212    |  P<0.001 **   P=0.060      P=0.013 *    P=0.002 ** |
|COCHRAN-ARMITAGE       |  P=0.120                                           |  P=0.002 **                                        |
|FISHER EXACT           |                 (e)        P=0.168      P=0.248    |               P=0.076      P=0.014 *    P=0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    1/75 (1%)    3/60 (5%)  |  0/60 (0%)    1/45 (2%)    2/75 (3%)    4/60 (7%)  |
|ADJUSTED (b)           |   0.0%         0.0%         1.5%        13.9%      |   0.0%         2.6%         6.3%        17.5%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    1/39 (3%)    2/32 (6%)    1/10 (10%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          341          324       |   ---          421 (T)      421 (T)      338       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.001 **     (e)        P=0.522      P=0.015 *  |  P<0.001 **   P=0.417      P=0.118      P=0.007 ** |
|INCIDENTAL TUMOR       |  P=0.654N       (e)        P=1.000        (e)      |  P=0.009 **   P=0.417      P=0.118      P=0.164    |
|LOGISTIC REGRESSION    |  P=0.075        (e)        P=0.650      P=0.159    |  P=0.013 *    P=0.417      P=0.118      P=0.065    |
|COCHRAN-ARMITAGE       |  P=0.023 *                                         |  P=0.029 *                                         |
|FISHER EXACT           |                 (e)        P=0.556      P=0.122    |               P=0.429      P=0.307      P=0.059    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  13
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    4/75 (5%)    5/60 (8%)  |  0/60 (0%)    3/45 (7%)    9/75 (12%)  13/60 (22%) |
|ADJUSTED (b)           |   0.0%         0.0%         7.4%        44.4%      |   0.0%         7.7%        22.2%        55.8%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    3/50 (6%)    0/0        |  0/59 (0%)    3/39 (8%)    5/32 (16%)   4/10 (40%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          341          324       |   ---          421 (T)      363          229       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.052      P<0.001 ** |  P<0.001 **   P=0.060      P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.077        (e)        P=0.092        (e)      |  P<0.001 **   P=0.060      P=0.004 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.007 **     (e)        P=0.094      P=0.017 *  |  P<0.001 **   P=0.060      P=0.003 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.007 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |                 (e)        P=0.092      P=0.029 *  |               P=0.076      P=0.004 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Pharynx                                                                                                                          |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    1/75 (1%)    1/60 (2%)  |  0/60 (0%)    0/45 (0%)    2/75 (3%)    3/60 (5%)  |
|ADJUSTED (b)           |   0.0%         0.0%         1.5%         3.7%      |   0.0%         0.0%         6.3%        15.4%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    0/39 (0%)    2/32 (6%)    1/10 (10%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          341          338       |   ---          ---          421 (T)      343       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.108        (e)        P=0.522      P=0.341    |  P<0.001 **     (e)        P=0.118      P=0.015 *  |
|INCIDENTAL TUMOR       |  P=0.446N       (e)        P=1.000        (e)      |  P=0.007 **     (e)        P=0.118      P=0.164    |
|LOGISTIC REGRESSION    |  P=0.425        (e)        P=0.650      P=0.745    |  P=0.011 *      (e)        P=0.118      P=0.094    |
|COCHRAN-ARMITAGE       |  P=0.262                                           |  P=0.034 *                                         |
|FISHER EXACT           |                 (e)        P=0.556      P=0.500    |                 (e)        P=0.307      P=0.122    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  14
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pharynx                                                                                                                          |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    2/75 (3%)    2/60 (3%)  |  0/60 (0%)    1/45 (2%)    5/75 (7%)    4/60 (7%)  |
|ADJUSTED (b)           |   0.0%         0.0%         4.0%        35.4%      |   0.0%         2.6%        11.6%        26.3%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    2/50 (4%)    0/0        |  0/59 (0%)    1/39 (3%)    2/32 (6%)    2/10 (20%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      324       |   ---          421 (T)      363          229       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.200      P=0.017 *  |  P<0.001 **   P=0.417      P=0.014 *    P=0.001 ** |
|INCIDENTAL TUMOR       |  P=0.042 *      (e)        P=0.200        (e)      |  P=0.036 *    P=0.417      P=0.113      P=0.010 ** |
|LOGISTIC REGRESSION    |  P=0.036 *      (e)        P=0.200      P=0.212    |  P=0.033 *    P=0.417      P=0.048 *    P=0.062    |
|COCHRAN-ARMITAGE       |  P=0.102                                           |  P=0.046 *                                         |
|FISHER EXACT           |                 (e)        P=0.307      P=0.248    |               P=0.429      P=0.050 *    P=0.059    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    2/45 (4%)    4/75 (5%)    1/60 (2%)  |  3/58 (5%)    1/45 (2%)    4/75 (5%)    0/60 (0%)  |
|ADJUSTED (b)           |   1.7%         4.9%         7.4%         2.4%      |   5.3%         2.6%         9.5%         0.0%      |
|TERMINAL (d)           |  1/60 (2%)    2/41 (5%)    3/50 (6%)    0/0        |  3/57 (5%)    1/39 (3%)    2/32 (6%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   419 (T)      419 (T)      343          303       |   421 (T)      421 (T)      363          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.057      P=0.369      P=0.147      P=0.424    |  P=0.604N     P=0.449N     P=0.284      P=0.534N   |
|INCIDENTAL TUMOR       |  P=0.521      P=0.369      P=0.244        (e)      |  P=0.203N     P=0.449N     P=0.612      P=0.534N   |
|LOGISTIC REGRESSION    |  P=0.515      P=0.369      P=0.246      P=0.875N   |  P=0.245N     P=0.449N     P=0.588      P=0.534N   |
|COCHRAN-ARMITAGE       |  P=0.526N                                          |  P=0.130N                                          |
|FISHER EXACT           |               P=0.393      P=0.260      P=0.752N   |               P=0.410N     P=0.641      P=0.116N   |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  15
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)   10/45 (22%)  52/75 (69%)  29/60 (48%) |  0/60 (0%)    3/45 (7%)    5/75 (7%)    5/60 (8%)  |
|ADJUSTED (b)           |   0.0%        24.4%        82.4%       100.0%      |   0.0%         7.7%        12.2%        30.8%      |
|TERMINAL (d)           |  0/60 (0%)   10/41 (24%)  39/50 (78%)   0/0        |  0/59 (0%)    3/39 (8%)    3/32 (9%)    2/10 (20%) |
|FIRST INCIDENCE (DAYS) |   ---          419 (T)      307          281       |   ---          421 (T)      338          370       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.060      P=0.013 *    P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **     (e)      |  P=0.011 *    P=0.060      P=0.039 *    P=0.013 *  |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.009 **   P=0.060      P=0.062      P=0.002 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.059                                           |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P=0.076      P=0.050 *    P=0.029 *  |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Carcinoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/45 (2%)    4/75 (5%)    2/60 (3%)  |  0/60 (0%)    0/45 (0%)    5/75 (7%)    4/60 (7%)  |
|ADJUSTED (b)           |   0.0%         2.4%         8.0%         5.9%      |   0.0%         0.0%        11.3%        14.9%      |
|TERMINAL (d)           |  0/60 (0%)    1/41 (2%)    4/50 (8%)    0/0        |  0/59 (0%)    0/39 (0%)    1/32 (3%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          419 (T)      419 (T)      296       |   ---          ---          315          336       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.424      P=0.043 *    P=0.127    |  P<0.001 **     (e)        P=0.015 *    P=0.010 ** |
|INCIDENTAL TUMOR       |  P=0.036 *    P=0.424      P=0.043 *      (e)      |  P=0.433        (e)        P=0.319      P=0.983    |
|LOGISTIC REGRESSION    |  P=0.075      P=0.424      P=0.043 *    P=0.577    |  P=0.040 *      (e)        P=0.063      P=0.098    |
|COCHRAN-ARMITAGE       |  P=0.214                                           |  P=0.024 *                                         |
|FISHER EXACT           |               P=0.429      P=0.092      P=0.248    |                 (e)        P=0.050 *    P=0.059    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  16
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    1/45 (2%)    8/75 (11%)   5/60 (8%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   1.7%         2.4%        15.4%        44.0%      |   0.0%         0.0%         0.0%        10.0%      |
|TERMINAL (d)           |  1/60 (2%)    1/41 (2%)    7/50 (14%)   0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    1/10 (10%) |
|FIRST INCIDENCE (DAYS) |   419 (T)      419 (T)      379          338       |   ---          ---          ---          421 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.674      P=0.010 *    P<0.001 ** |  P=0.037 *      (e)          (e)        P=0.157    |
|INCIDENTAL TUMOR       |  P=0.002 **   P=0.674      P=0.018 *      (e)      |  P=0.037 *      (e)          (e)        P=0.157    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.674      P=0.020 *    P=0.008 ** |  P=0.037 *      (e)          (e)        P=0.157    |
|COCHRAN-ARMITAGE       |  P=0.060                                           |  P=0.209                                           |
|FISHER EXACT           |               P=0.676      P=0.036 *    P=0.103    |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/45 (4%)   10/75 (13%)  13/60 (22%) |  0/60 (0%)    2/45 (4%)    4/75 (5%)    7/60 (12%) |
|ADJUSTED (b)           |   0.0%         4.7%        19.5%        64.1%      |   0.0%         5.1%        11.7%        40.5%      |
|TERMINAL (d)           |  0/60 (0%)    1/41 (2%)    9/50 (18%)   0/0        |  0/59 (0%)    2/39 (5%)    3/32 (9%)    3/10 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          391          406          211       |   ---          421 (T)      406          338       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.165      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.153      P=0.016 *    P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.424      P=0.001 **     (e)      |  P<0.001 **   P=0.153      P=0.039 *    P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.202      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.153      P=0.027 *    P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.005 **                                        |
|FISHER EXACT           |               P=0.181      P=0.002 **   P<0.001 ** |               P=0.181      P=0.092      P=0.006 ** |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  17
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/45 (4%)   17/75 (23%)  27/60 (45%) |  0/60 (0%)    3/45 (7%)    9/75 (12%)  12/60 (20%) |
|ADJUSTED (b)           |   0.0%         4.7%        32.0%       100.0%      |   0.0%         7.7%        24.4%        52.0%      |
|TERMINAL (d)           |  0/60 (0%)    1/41 (2%)   14/50 (28%)   0/0        |  0/59 (0%)    3/39 (8%)    6/32 (19%)   3/10 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          391          405          211       |   ---          421 (T)      391          264       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.165      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.060      P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.424      P<0.001 **     (e)      |  P<0.001 **   P=0.060      P=0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.202      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.060      P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.181      P<0.001 **   P<0.001 ** |               P=0.076      P=0.004 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    8/75 (11%)  15/60 (25%) |  0/60 (0%)    1/45 (2%)    6/75 (8%)    5/60 (8%)  |
|ADJUSTED (b)           |   0.0%         0.0%        15.2%       100.0%      |   0.0%         2.6%        16.4%        19.0%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    6/50 (12%)   0/0        |  0/59 (0%)    1/39 (3%)    4/32 (13%)   0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          405          238       |   ---          421 (T)      391          264       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.003 **   P<0.001 ** |  P<0.001 **   P=0.417      P=0.003 **   P=0.002 ** |
|INCIDENTAL TUMOR       |  P<0.001 **     (e)        P=0.010 **     (e)      |  P=0.035 *    P=0.417      P=0.013 *    P=0.846    |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)        P=0.005 **   P<0.001 ** |  P=0.011 *    P=0.417      P=0.010 *    P=0.056    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.022 *                                         |
|FISHER EXACT           |                 (e)        P=0.008 **   P<0.001 ** |               P=0.429      P=0.027 *    P=0.029 *  |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  18
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)   11/45 (24%)  54/75 (72%)  30/60 (50%) |  0/60 (0%)    3/45 (7%)   10/75 (13%)   9/60 (15%) |
|ADJUSTED (b)           |   0.0%        26.8%        85.6%       100.0%      |   0.0%         7.7%        22.4%        41.1%      |
|TERMINAL (d)           |  0/60 (0%)   11/41 (27%)  41/50 (82%)   0/0        |  0/59 (0%)    3/39 (8%)    4/32 (13%)   2/10 (20%) |
|FIRST INCIDENCE (DAYS) |   ---          419 (T)      307          281       |   ---          421 (T)      315          336       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.060      P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **     (e)      |  P=0.017 *    P=0.060      P=0.013 *    P=0.013 *  |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.001 **   P=0.060      P=0.005 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.004 **                                        |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P=0.076      P=0.002 **   P=0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)   13/45 (29%)  60/75 (80%)  40/60 (67%) |  0/60 (0%)    6/45 (13%)  18/75 (24%)  20/60 (33%) |
|ADJUSTED (b)           |   1.7%        30.9%        93.7%       100.0%      |   0.0%        15.4%        41.7%        73.7%      |
|TERMINAL (d)           |  1/60 (2%)   12/41 (29%)  46/50 (92%)   0/0        |  0/59 (0%)    6/39 (15%)  10/32 (31%)   5/10 (50%) |
|FIRST INCIDENCE (DAYS) |   419 (T)      391          307          211       |   ---          421 (T)      315          264       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.004 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **     (e)      |  P<0.001 **   P=0.004 **   P<0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.004 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P=0.005 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  19
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Sebaceous Gland                                                                                                            |
|     Carcinoma, Basal Cell Carcinoma or Adenoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    7/75 (9%)    5/60 (8%)  |  0/60 (0%)    0/45 (0%)    1/75 (1%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%        13.3%        21.9%      |   0.0%         0.0%         3.1%         7.7%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    5/50 (10%)   0/0        |  0/59 (0%)    0/39 (0%)    1/32 (3%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          405          280       |   ---          ---          421 (T)      406       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.006 **   P=0.001 ** |  P=0.040 *      (e)        P=0.378      P=0.203    |
|INCIDENTAL TUMOR       |  P=0.039 *      (e)        P=0.021 *      (e)      |  P=0.222        (e)        P=0.378      P=0.983    |
|LOGISTIC REGRESSION    |  P=0.003 **     (e)        P=0.010 **   P=0.058    |  P=0.090        (e)        P=0.378      P=0.363    |
|COCHRAN-ARMITAGE       |  P=0.013 *                                         |  P=0.262                                           |
|FISHER EXACT           |                 (e)        P=0.014 *    P=0.029 *  |                 (e)        P=0.556      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    2/60 (3%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%       100.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          350       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)          (e)        P=0.001 ** |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.232        (e)          (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.042 *      (e)          (e)        P=0.080    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.049 *                                         |    (e)                                             |
|FISHER EXACT           |                 (e)          (e)        P=0.248    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  20
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/45 (0%)    0/75 (0%)    2/60 (3%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   1.7%         0.0%         0.0%       100.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/60 (2%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   419 (T)      ---          ---          350       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.007 **   P=0.576N     P=0.536N     P=0.001 ** |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.452      P=0.576N     P=0.536N       (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.170      P=0.576N     P=0.536N     P=0.152    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.249                                           |    (e)                                             |
|FISHER EXACT           |               P=0.571N     P=0.444N     P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 24/60 (40%)  26/45 (58%)  26/75 (35%)   2/60 (3%)  |                                                    |
|ADJUSTED (b)           |  40.0%        61.9%        45.9%        13.1%      |                                                    |
|TERMINAL (d)           | 24/60 (40%)  25/41 (61%)  20/50 (40%)   0/0        |                                                    |
|FIRST INCIDENCE (DAYS) |   419 (T)      405          341          348       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.043 *    P=0.020 *    P=0.186      P=0.026 *  |                                                    |
|INCIDENTAL TUMOR       |  P=0.237N     P=0.031 *    P=0.577        (e)      |                                                    |
|LOGISTIC REGRESSION    |  P=0.453N     P=0.025 *    P=0.497      P=0.802N   |                                                    |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |                                                    |
|FISHER EXACT           |               P=0.054      P=0.323N     P<0.001N** |                                                    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  21
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/44 (2%)    3/75 (4%)    1/60 (2%)  |  1/60 (2%)    1/45 (2%)    2/74 (3%)    1/60 (2%)  |
|ADJUSTED (b)           |   3.3%         2.4%         5.5%       100.0%      |   1.7%         2.6%         5.4%         2.1%      |
|TERMINAL (d)           |  2/60 (3%)    1/41 (2%)    2/50 (4%)    0/0        |  1/59 (2%)    1/39 (3%)    1/32 (3%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   419 (T)      419 (T)      379          384       |   421 (T)      421 (T)      405          296       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.063      P=0.631N     P=0.437      P<0.001 ** |  P=0.236      P=0.666      P=0.324      P=0.558    |
|INCIDENTAL TUMOR       |  P=0.421      P=0.631N     P=0.627        (e)      |  P=0.662      P=0.666      P=0.591      P=0.843N   |
|LOGISTIC REGRESSION    |  P=0.340      P=0.631N     P=0.559      P=0.429    |  P=0.646      P=0.666      P=0.424      P=0.673N   |
|COCHRAN-ARMITAGE       |  P=0.429N                                          |  P=0.612N                                          |
|FISHER EXACT           |               P=0.616N     P=0.605      P=0.500N   |               P=0.676      P=0.579      P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Tongue                                                                                                                           |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    2/60 (3%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%        10.6%      |   0.0%         2.6%         0.0%         2.4%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    0/50 (0%)    0/0        |  0/59 (0%)    1/39 (3%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          324       |   ---          421 (T)      ---          338       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006 **     (e)          (e)        P=0.055    |  P=0.239      P=0.417        (e)        P=0.424    |
|INCIDENTAL TUMOR       |  P=0.554        (e)          (e)          (e)      |  P=0.577      P=0.417        (e)        P=1.000    |
|LOGISTIC REGRESSION    |  P=0.100        (e)          (e)        P=0.353    |  P=0.508      P=0.417        (e)        P=0.724    |
|COCHRAN-ARMITAGE       |  P=0.049 *                                         |  P=0.449                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.248    |               P=0.429        (e)        P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  22
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tongue                                                                                                                           |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    1/75 (1%)    2/60 (3%)  |  0/60 (0%)    2/45 (4%)    2/75 (3%)    8/60 (13%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.0%        10.6%      |   0.0%         5.1%         5.3%        36.1%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    1/50 (2%)    0/0        |  0/59 (0%)    2/39 (5%)    1/32 (3%)    2/10 (20%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      324       |   ---          421 (T)      391          285       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002 **     (e)        P=0.464      P=0.055    |  P<0.001 **   P=0.153      P=0.149      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.287        (e)        P=0.464        (e)      |  P<0.001 **   P=0.153      P=0.357      P=0.013 *  |
|LOGISTIC REGRESSION    |  P=0.094        (e)        P=0.464      P=0.353    |  P<0.001 **   P=0.153      P=0.239      P=0.002 ** |
|COCHRAN-ARMITAGE       |  P=0.079                                           |  P=0.001 **                                        |
|FISHER EXACT           |                 (e)        P=0.556      P=0.248    |               P=0.181      P=0.307      P=0.003 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Tongue                                                                                                                           |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    1/75 (1%)    0/60 (0%)  |  0/60 (0%)    2/45 (4%)    2/75 (3%)    7/60 (12%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.0%         0.0%      |   0.0%         5.1%         5.3%        34.5%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    1/50 (2%)    0/0        |  0/59 (0%)    2/39 (5%)    1/32 (3%)    2/10 (20%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      ---       |   ---          421 (T)      391          285       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.518        (e)        P=0.464        (e)      |  P<0.001 **   P=0.153      P=0.149      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.518        (e)        P=0.464        (e)      |  P=0.001 **   P=0.153      P=0.357      P=0.013 *  |
|LOGISTIC REGRESSION    |  P=0.518        (e)        P=0.464        (e)      |  P<0.001 **   P=0.153      P=0.239      P=0.002 ** |
|COCHRAN-ARMITAGE       |  P=0.736                                           |  P=0.003 **                                        |
|FISHER EXACT           |                 (e)        P=0.556        (e)      |               P=0.181      P=0.307      P=0.006 ** |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  23
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 11/60 (18%)   9/45 (20%)   3/75 (4%)    1/60 (2%)  |
|ADJUSTED (b)           |                                                    |  18.6%        22.4%         7.1%         6.3%      |
|TERMINAL (d)           |                                                    | 11/59 (19%)   8/39 (21%)   1/32 (3%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   421 (T)      391          338          405       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.140N     P=0.397      P=0.168N     P=0.395N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.012N*    P=0.479      P=0.043N*    P=0.170N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.016N*    P=0.471      P=0.032N*    P=0.246N   |
|COCHRAN-ARMITAGE       |                                                    |  P<0.001N**                                        |
|FISHER EXACT           |                                                    |               P=0.511      P=0.007N**   P=0.002N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 11/60 (18%)  10/45 (22%)   4/75 (5%)    1/60 (2%)  |
|ADJUSTED (b)           |                                                    |  18.6%        24.9%        10.1%         6.3%      |
|TERMINAL (d)           |                                                    | 11/59 (19%)   9/39 (23%)   2/32 (6%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   421 (T)      391          338          405       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.183N     P=0.290      P=0.287N     P=0.395N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.021N*    P=0.362      P=0.104N     P=0.170N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.024N*    P=0.354      P=0.075N     P=0.246N   |
|COCHRAN-ARMITAGE       |                                                    |  P<0.001N**                                        |
|FISHER EXACT           |                                                    |               P=0.400      P=0.017N*    P=0.002N** |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  24
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    1/45 (2%)   13/75 (17%)  16/60 (27%) |  0/60 (0%)    4/45 (9%)   11/75 (15%)  12/60 (20%) |
|ADJUSTED (b)           |   1.7%         2.4%        23.9%       100.0%      |   0.0%        10.3%        24.4%        49.6%      |
|TERMINAL (d)           |  1/60 (2%)    1/41 (2%)   10/50 (20%)   0/0        |  0/59 (0%)    4/39 (10%)   5/32 (16%)   3/10 (30%) |
|FIRST INCIDENCE (DAYS) |   419 (T)      419 (T)      378          254       |   ---          421 (T)      338          251       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.674      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.024 *    P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.674      P=0.002 **     (e)      |  P=0.002 **   P=0.024 *    P=0.004 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.674      P=0.001 **   P<0.001 ** |  P<0.001 **   P=0.024 *    P=0.003 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.676      P=0.002 **   P<0.001 ** |               P=0.031 *    P=0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/45 (4%)   21/75 (28%)  23/60 (38%) |  0/60 (0%)    2/45 (4%)   22/75 (29%)  35/60 (58%) |
|ADJUSTED (b)           |   0.0%         4.6%        30.8%        67.9%      |   0.0%         4.5%        35.0%        77.1%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    6/50 (12%)   0/0        |  0/59 (0%)    0/39 (0%)    1/32 (3%)    3/10 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          359          229          209       |   ---          357          184          229       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.170      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.176      P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.493N       (e)        P=0.010 **     (e)      |  P=0.002 **   P=0.814      P=0.190      P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.009 **   P=0.265      P=0.003 **   P=0.056    |  P<0.001 **   P=0.821      P=0.012 *    P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.181      P<0.001 **   P<0.001 ** |               P=0.181      P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  25
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    3/45 (7%)   32/75 (43%)  36/60 (60%) |  0/60 (0%)    6/45 (13%)  32/75 (43%)  42/60 (70%) |
|ADJUSTED (b)           |   1.7%         6.9%        46.8%       100.0%      |   0.0%        14.3%        50.4%        86.4%      |
|TERMINAL (d)           |  1/60 (2%)    1/41 (2%)   15/50 (30%)   0/0        |  0/59 (0%)    4/39 (10%)   6/32 (19%)   5/10 (50%) |
|FIRST INCIDENCE (DAYS) |   419 (T)      359          229          209       |   ---          357          184          229       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.192      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.005 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.006 **   P=0.674      P<0.001 **     (e)      |  P<0.001 **   P=0.022 *    P<0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.280      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.023 *    P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.209      P<0.001 **   P<0.001 ** |               P=0.005 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/45 (2%)    1/75 (1%)    1/60 (2%)  |  1/60 (2%)    3/45 (7%)    6/75 (8%)    4/60 (7%)  |
|ADJUSTED (b)           |   0.0%         2.2%         2.0%         2.6%      |   1.7%         7.7%        16.2%        23.8%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    1/50 (2%)    0/0        |  0/59 (0%)    3/39 (8%)    4/32 (13%)   1/10 (10%) |
|FIRST INCIDENCE (DAYS) |   ---          250          419 (T)      308       |   390          421 (T)      363          364       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.231      P=0.443      P=0.464      P=0.409    |  P<0.001 **   P=0.181      P=0.015 *    P=0.007 ** |
|INCIDENTAL TUMOR       |  P=0.445N       (e)        P=0.464        (e)      |  P=0.141      P=0.303      P=0.115      P=0.842N   |
|LOGISTIC REGRESSION    |  P=0.631N       (e)        P=0.464      P=0.902    |  P=0.028 *    P=0.276      P=0.058      P=0.060    |
|COCHRAN-ARMITAGE       |  P=0.438                                           |  P=0.214                                           |
|FISHER EXACT           |               P=0.429      P=0.556      P=0.500    |               P=0.209      P=0.102      P=0.182    |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  26
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    2/75 (3%)    0/60 (0%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         3.5%         0.0%      |   0.0%         2.2%         0.0%         0.0%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    1/50 (2%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          355          ---       |   ---          357          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.262        (e)        P=0.228        (e)      |  P=0.640N     P=0.443        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.632N       (e)        P=0.464        (e)      |  P=0.128N       (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.672        (e)        P=0.316        (e)      |  P=0.421N       (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.649                                           |  P=0.536N                                          |
|FISHER EXACT           |                 (e)        P=0.307        (e)      |               P=0.429        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    2/75 (3%)    0/60 (0%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         3.5%         0.0%      |   0.0%         2.2%         0.0%         0.0%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    1/50 (2%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          355          ---       |   ---          357          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.262        (e)        P=0.228        (e)      |  P=0.640N     P=0.443        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.632N       (e)        P=0.464        (e)      |  P=0.128N       (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.672        (e)        P=0.316        (e)      |  P=0.421N       (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.649                                           |  P=0.536N                                          |
|FISHER EXACT           |                 (e)        P=0.307        (e)      |               P=0.429        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  27
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    3/75 (4%)    4/60 (7%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         6.0%        70.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/60 (0%)    0/41 (0%)    3/50 (6%)    0/0        |  0/59 (0%)    0/39 (0%)    0/32 (0%)    0/10 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          419 (T)      308       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.092      P<0.001 ** |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.004 **     (e)        P=0.092        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.002 **     (e)        P=0.092      P=0.011 *  |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.015 *                                         |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.168      P=0.059    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 28/60 (47%)  34/45 (76%)  66/75 (88%)  47/60 (78%) | 17/60 (28%)  24/45 (53%)  54/75 (72%)  41/60 (68%) |
|ADJUSTED (b)           |  46.7%        81.0%        97.1%       100.0%      |  28.8%        55.8%        92.5%       100.0%      |
|TERMINAL (d)           | 28/60 (47%)  33/41 (80%)  48/50 (96%)   0/0        | 17/59 (29%)  20/39 (51%)  28/32 (88%)  10/10 (100%)|
|FIRST INCIDENCE (DAYS) |   419 (T)      405          307          226       |   421 (T)      391          229          229       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **     (e)      |  P<0.001 **   P=0.012 *    P<0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.009 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.002 **   P<0.001 **   P<0.001 ** |               P=0.008 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  28
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      0.003        0.007        0.015     |   CONTROL      0.003        0.007        0.015     |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    6/45 (13%)  48/75 (64%)  50/60 (83%) |  1/60 (2%)   14/45 (31%)  49/75 (65%)  56/60 (93%) |
|ADJUSTED (b)           |   1.7%        13.3%        69.1%        97.1%      |   1.7%        33.0%        72.2%        98.2%      |
|TERMINAL (d)           |  1/60 (2%)    2/41 (5%)   29/50 (58%)   0/0        |  0/59 (0%)   11/39 (28%)  14/32 (44%)   9/10 (90%) |
|FIRST INCIDENCE (DAYS) |   419 (T)      250          229          209       |   390          357          184          229       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.022 *    P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.369      P<0.001 **     (e)      |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.369      P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.023 *    P<0.001 **   P<0.001 ** |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 28/60 (47%)  38/45 (84%)  73/75 (97%)  58/60 (97%) | 18/60 (30%)  33/45 (73%)  71/75 (95%)  58/60 (97%) |
|ADJUSTED (b)           |  46.7%        84.4%       100.0%       100.0%      |  30.0%        73.3%        97.3%       100.0%      |
|TERMINAL (d)           | 28/60 (47%)  34/41 (83%)  50/50 (100%)  0/0        | 17/59 (29%)  27/39 (69%)  30/32 (94%)  10/10 (100%)|
|FIRST INCIDENCE (DAYS) |   419 (T)      250          229          209       |   390          357          184          229       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **     (e)      |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.057    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/18/94                     EXPERIMENT: 05166 TEST: 01                                                 PAGE  29
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHYLBENZIDINE DIHYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 60 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 61 WEEKS
 
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (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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