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TDMS Study 05172-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: HLA, VA                                     3,3-DIMETHOXYBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94       
EXPERIMENT: 05172 TEST: 01                                                                                     TIME: 06:46:29       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99989        
PATHOLOGIST: B. ULLAND                                                                                         CAS: 20325400        
------------------------------------------------------------------------------------------------------------------------------------
               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-DIMETHOXYBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94      
EXPERIMENT: 05172 TEST: 01                                                                                     TIME: 06:46:29      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99989       
PATHOLOGIST: B. ULLAND                                                                                         CAS: 20325400       
                                                    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-DIMETHOXYBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94       
EXPERIMENT: 05172 TEST: 01                                                                                     TIME: 06:46:29       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99989        
PATHOLOGIST: B. ULLAND                                                                                         CAS: 20325400        
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                             IN THE ANALYSIS OF THE STUDY OF 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
              ====================================================================================================
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma Malignant
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Brain                         Astrocytoma Malignant
                             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 Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          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
                             Pancreas                      Adenoma
                             Pharynx                       Squamous Cell Papilloma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Salivary Glands               Schwannoma Malignant
                             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: Subcutaneous Tissue     Fibroma
                                                           Neurofibroma
                                                           Neurofibroma or Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                             Testes                        Adenoma
                             Thyroid Gland: C-Cell         Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: HLA, VA                                     3,3-DIMETHOXYBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94       
EXPERIMENT: 05172 TEST: 01                                                                                     TIME: 06:46:29       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99989        
PATHOLOGIST: B. ULLAND                                                                                         CAS: 20325400        
                             Thyroid Gland: Follicular Cell
                                                           Carcinoma or Adenoma
                             Tongue                        Squamous Cell Carcinoma or Papilloma Squamous
                                                           Squamous Cell Papilloma
                             Zymbal's Gland                Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Mesothelioma Benign, Malignant, NOS
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
              ====================================================================================================
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             Intestine Large               Carcinoma or Adenoma
                                                           Polyp Adenomatous
                             Intestine Small               Carcinoma
                                                           Carcinoma or Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Mammary Gland                 Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                                                           Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                                                           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 Papilloma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Skin                          Basal Cell Adenoma
                                                           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
                             Thyroid Gland: Follicular Cell
                                                           Carcinoma or Adenoma
                             Tongue                        Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma or Papilloma Squamous
                                                           Squamous Cell Papilloma
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: HLA, VA                                     3,3-DIMETHOXYBENZIDINE DIHYDROCHLORIDE                        DATE: 09/18/94       
EXPERIMENT: 05172 TEST: 01                                                                                     TIME: 06:46:29       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1ES9565503          ROUTE: DOSED WATER                                                                 NTP C#: 99989        
PATHOLOGIST: B. ULLAND                                                                                         CAS: 20325400        
                             Uterus                        Adenoma
                                                           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: 05172 TEST: 01                                                 PAGE   1
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/60 (23%)  17/44 (39%)  23/74 (31%)   9/60 (15%) |  5/60 (8%)    1/45 (2%)    1/74 (1%)    0/59 (0%)  |
|ADJUSTED (b)           |  28.6%        69.0%       100.0%        73.0%      |  10.5%         6.7%         5.6%         0.0%      |
|TERMINAL (d)           | 10/44 (23%)   3/8 (38%)    0/0          0/0        |  4/45 (9%)    1/15 (7%)    0/5 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   573          480          417          527       |   574          648 (T)      562          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.601N     P=0.462N     P=0.652      P=0.936N   |
|INCIDENTAL TUMOR       |  P=0.148N     P=0.328      P=0.523      P=0.466N   |  P=0.288N     P=0.358N     P=0.437N     P=0.500N   |
|LOGISTIC REGRESSION    |  P=0.540      P=0.018 *    P=0.007 **   P=0.653N   |  P=0.247N     P=0.298N     P=0.470N     P=0.490N   |
|COCHRAN-ARMITAGE       |  P=0.077N                                          |  P=0.012N*                                         |
|FISHER EXACT           |               P=0.071      P=0.211      P=0.177N   |               P=0.184N     P=0.063N     P=0.030N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/44 (2%)    3/74 (4%)    0/60 (0%)  |  0/60 (0%)    0/45 (0%)    0/74 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   4.1%         2.9%        43.8%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/44 (2%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/5 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   603          556          557          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.102      P=0.672      P=0.006 **     (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.294N     P=0.387N     P=0.644N     P=0.362N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.654N     P=0.609N     P=0.171      P=0.706N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.213N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.616N     P=0.599      P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE   2
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 15/60 (25%)  18/44 (41%)  23/74 (31%)   9/60 (15%) |  5/60 (8%)    1/45 (2%)    1/74 (1%)    0/59 (0%)  |
|ADJUSTED (b)           |  29.9%        69.9%       100.0%        73.0%      |  10.5%         6.7%         5.6%         0.0%      |
|TERMINAL (d)           | 10/44 (23%)   3/8 (38%)    0/0          0/0        |  4/45 (9%)    1/15 (7%)    0/5 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   573          480          417          527       |   574          648 (T)      562          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.601N     P=0.462N     P=0.652      P=0.936N   |
|INCIDENTAL TUMOR       |  P=0.076N     P=0.445      P=0.528N     P=0.274N   |  P=0.288N     P=0.358N     P=0.437N     P=0.500N   |
|LOGISTIC REGRESSION    |  P=0.396N     P=0.215      P=0.013 *    P=0.444N   |  P=0.247N     P=0.298N     P=0.470N     P=0.490N   |
|COCHRAN-ARMITAGE       |  P=0.047N*                                         |  P=0.012N*                                         |
|FISHER EXACT           |               P=0.066      P=0.280      P=0.127N   |               P=0.184N     P=0.063N     P=0.030N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Astrocytoma Malignant                                                                                                       |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/44 (5%)    3/75 (4%)    1/60 (2%)  |  0/60 (0%)    1/45 (2%)    1/75 (1%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        19.6%        54.3%         3.3%      |   0.0%         3.7%        16.7%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    1/7 (14%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    1/6 (17%)    0/0        |
|FIRST INCIDENCE (DAYS) |   ---          618          536          506       |   ---          602          648 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002 **   P=0.021 *    P=0.004 **   P=0.372    |  P=0.206      P=0.373      P=0.118        (e)      |
|INCIDENTAL TUMOR       |  P=0.510      P=0.138      P=0.508      P=0.912    |  P=0.509      P=0.609      P=0.118        (e)      |
|LOGISTIC REGRESSION    |  P=0.143      P=0.073      P=0.057      P=0.594    |  P=0.371      P=0.460      P=0.118        (e)      |
|COCHRAN-ARMITAGE       |  P=0.480                                           |  P=0.567N                                          |
|FISHER EXACT           |               P=0.177      P=0.168      P=0.500    |               P=0.429      P=0.556        (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE   3
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/60 (23%)   6/43 (14%)  19/73 (26%)  12/59 (20%) |  5/58 (9%)   15/44 (34%)  13/74 (18%)  16/55 (29%) |
|ADJUSTED (b)           |  28.7%        34.7%        80.5%        80.5%      |  11.4%        61.7%        43.4%       100.0%      |
|TERMINAL (d)           | 10/44 (23%)   1/8 (13%)    0/0          0/0        |  5/44 (11%)   7/15 (47%)   0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   531          485          333          423       |   648 (T)      436          358          262       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.202      P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.233      P=0.458N     P=0.284      P=0.340    |  P=0.012 *    P<0.001 **   P=0.258      P=0.006 ** |
|LOGISTIC REGRESSION    |  P=0.076      P=0.307N     P=0.107      P=0.196    |  P=0.002 **   P<0.001 **   P=0.133      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.539                                           |  P=0.036 *                                         |
|FISHER EXACT           |               P=0.176N     P=0.439      P=0.431N   |               P=0.002 **   P=0.108      P=0.005 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    6/43 (14%)  15/73 (21%)  19/59 (32%) |  2/58 (3%)   17/44 (39%)  41/74 (55%)  30/55 (55%) |
|ADJUSTED (b)           |   3.9%        37.7%        43.4%        50.1%      |   4.5%        59.3%        88.3%        79.6%      |
|TERMINAL (d)           |  0/44 (0%)    1/8 (13%)    0/0          0/0        |  2/44 (5%)    5/15 (33%)   3/6 (50%)    0/0        |
|FIRST INCIDENCE (DAYS) |   603          603          284          267       |   648 (T)      373          220          270       |
|-----------------------|                                                    |                                                    |
|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=0.021 *    P=0.520      P=0.458      P=0.267    |  P=0.001 **   P<0.001 **   P<0.001 **   P=0.007 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.020 *    P=0.011 *    P=0.003 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.004 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.054      P=0.002 **   P<0.001 ** |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE   4
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/60 (27%)  12/43 (28%)  33/73 (45%)  29/59 (49%) |  7/58 (12%)  27/44 (61%)  48/74 (65%)  41/55 (75%) |
|ADJUSTED (b)           |  31.6%        60.7%        89.3%        89.3%      |  15.9%        83.6%        91.7%       100.0%      |
|TERMINAL (d)           | 10/44 (23%)   2/8 (25%)    0/0          0/0        |  7/44 (16%)  10/15 (67%)   3/6 (50%)    0/0        |
|FIRST INCIDENCE (DAYS) |   531          485          284          267       |   648 (T)      373          220          262       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.017 *    P=0.565N     P=0.204      P=0.179    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.001 **   P=0.298      P=0.007 **   P=0.036 *  |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.003 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.532      P=0.021 *    P=0.009 ** |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    4/75 (5%)    3/60 (5%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%        19.5%         8.6%      |   0.0%         6.7%         0.0%        14.3%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          485          414       |   ---          648 (T)      ---          563       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002 **     (e)        P=0.009 **   P=0.056    |  P=0.015 *    P=0.282        (e)        P=0.108    |
|INCIDENTAL TUMOR       |  P=0.273        (e)        P=0.451      P=0.661    |  P=0.098      P=0.282        (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.083        (e)        P=0.095      P=0.249    |  P=0.086      P=0.282        (e)        P=0.347    |
|COCHRAN-ARMITAGE       |  P=0.045 *                                         |  P=0.433                                           |
|FISHER EXACT           |                 (e)        P=0.092      P=0.122    |               P=0.429        (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE   5
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large: Colon                                                                                                           |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    4/75 (5%)    2/60 (3%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%        19.5%         6.5%      |   0.0%         6.7%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          485          414       |   ---          648 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006 **     (e)        P=0.009 **   P=0.131    |  P=0.732      P=0.282        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.415        (e)        P=0.451      P=0.769    |  P=0.732      P=0.282        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.144        (e)        P=0.095      P=0.368    |  P=0.732      P=0.282        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.113                                           |  P=0.531N                                          |
|FISHER EXACT           |                 (e)        P=0.092      P=0.248    |               P=0.429        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large: Colon                                                                                                           |
|     Polyp Adenomatous                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/45 (2%)    4/75 (5%)    4/60 (7%)  |  0/60 (0%)    0/45 (0%)    1/75 (1%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%        10.0%        25.3%        32.9%      |   0.0%         0.0%         2.1%         6.3%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          644          546          486       |   ---          ---          424          424       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.193      P=0.002 **   P<0.001 ** |  P=0.028 *      (e)        P=0.455      P=0.116    |
|INCIDENTAL TUMOR       |  P=0.056      P=0.741      P=0.401      P=0.237    |  P=0.260        (e)        P=0.897      P=0.730    |
|LOGISTIC REGRESSION    |  P=0.002 **   P=0.238      P=0.030 *    P=0.039 *  |  P=0.201        (e)        P=0.886      P=0.597    |
|COCHRAN-ARMITAGE       |  P=0.036 *                                         |  P=0.077                                           |
|FISHER EXACT           |               P=0.429      P=0.092      P=0.059    |                 (e)        P=0.556      P=0.248    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE   6
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    4/45 (9%)    7/75 (9%)    5/60 (8%)  |  0/60 (0%)    1/45 (2%)    1/75 (1%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%        26.7%        17.7%        19.6%      |   0.0%         6.7%         1.9%        18.4%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          354          417          267       |   ---          648 (T)      379          452       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.001 **   P=0.003 **   P=0.003 ** |  P=0.005 **   P=0.282      P=0.479      P=0.019 *  |
|INCIDENTAL TUMOR       |  P=0.572      P=0.299      P=0.326      P=0.371    |  P=0.110      P=0.282      P=0.897      P=0.424    |
|LOGISTIC REGRESSION    |  P=0.169      P=0.043 *    P=0.043 *    P=0.100    |  P=0.134      P=0.282      P=0.967      P=0.190    |
|COCHRAN-ARMITAGE       |  P=0.077                                           |  P=0.173                                           |
|FISHER EXACT           |               P=0.031 *    P=0.014 *    P=0.029 *  |               P=0.429      P=0.556      P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Duodenum                                                                                                        |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/45 (4%)    2/75 (3%)    0/60 (0%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%        12.1%         5.9%         0.0%      |   0.0%         0.0%         0.0%        14.3%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          354          485          ---       |   ---          ---          ---          563       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.387      P=0.073      P=0.147        (e)      |  P=0.022 *      (e)          (e)        P=0.108    |
|INCIDENTAL TUMOR       |  P=0.209N     P=0.514      P=0.662        (e)      |  P=0.154        (e)          (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.334N     P=0.210      P=0.360        (e)      |  P=0.072        (e)          (e)        P=0.347    |
|COCHRAN-ARMITAGE       |  P=0.463N                                          |  P=0.206                                           |
|FISHER EXACT           |               P=0.181      P=0.307        (e)      |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE   7
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/45 (4%)    5/75 (7%)    4/60 (7%)  |  0/60 (0%)    1/45 (2%)    1/75 (1%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%        16.7%        12.3%        17.5%      |   0.0%         6.7%         1.9%         4.8%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          638          417          267       |   ---          648 (T)      379          452       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.022 *    P=0.014 *    P=0.007 ** |  P=0.088      P=0.282      P=0.479      P=0.295    |
|INCIDENTAL TUMOR       |  P=0.415      P=0.529      P=0.451      P=0.414    |  P=0.392      P=0.282      P=0.897      P=0.887    |
|LOGISTIC REGRESSION    |  P=0.106      P=0.048 *    P=0.101      P=0.153    |  P=0.508      P=0.282      P=0.967      P=0.801    |
|COCHRAN-ARMITAGE       |  P=0.066                                           |  P=0.409                                           |
|FISHER EXACT           |               P=0.181      P=0.050 *    P=0.059    |               P=0.429      P=0.556      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Lipoma                                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/44 (0%)    0/74 (0%)    0/60 (0%)  |  2/60 (3%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.4%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  2/45 (4%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   648 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.566N     P=0.500N     P=0.721N       (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.566N     P=0.500N     P=0.721N       (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.566N     P=0.500N     P=0.721N       (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.098N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.324N     P=0.196N     P=0.248N   |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE   8
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    3/45 (7%)    7/74 (9%)    6/60 (10%) |  0/60 (0%)    1/44 (2%)    0/75 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%        17.9%        24.9%        39.8%      |   0.0%         6.7%         0.0%        51.3%      |
|TERMINAL (d)           |  0/44 (0%)    1/8 (13%)    0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          538          485          485       |   ---          648 (T)      ---          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.019 *    P<0.001 **   P<0.001 ** |  P=0.001 **   P=0.282        (e)        P=0.021 *  |
|INCIDENTAL TUMOR       |  P=0.043 *    P=0.100      P=0.236      P=0.145    |  P=0.044 *    P=0.282        (e)        P=0.424    |
|LOGISTIC REGRESSION    |  P=0.196      P=0.078      P=0.019 *    P=0.007 ** |  P=0.033 *    P=0.282        (e)        P=0.178    |
|COCHRAN-ARMITAGE       |  P=0.025 *                                         |  P=0.161                                           |
|FISHER EXACT           |               P=0.076      P=0.014 *    P=0.014 *  |               P=0.423        (e)        P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    1/45 (2%)    0/74 (0%)    2/60 (3%)  |  0/60 (0%)    0/44 (0%)    0/75 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   2.3%        12.5%         0.0%        15.4%      |   0.0%         0.0%         0.0%        25.0%      |
|TERMINAL (d)           |  1/44 (2%)    1/8 (13%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      647 (T)      ---          551       |   ---          ---          ---          602       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.001 **   P=0.352        (e)        P=0.020 *  |  P=0.008 **     (e)          (e)        P=0.050 *  |
|INCIDENTAL TUMOR       |  P=0.013 *    P=0.352        (e)        P=0.399    |  P=0.158        (e)          (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.052      P=0.352        (e)        P=0.257    |  P=0.026 *      (e)          (e)        P=0.166    |
|COCHRAN-ARMITAGE       |  P=0.405                                           |  P=0.207                                           |
|FISHER EXACT           |               P=0.676      P=0.448N     P=0.500    |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE   9
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    4/45 (9%)    7/74 (9%)    8/60 (13%) |  0/60 (0%)    1/44 (2%)    0/75 (0%)    3/60 (5%)  |
|ADJUSTED (b)           |   2.3%        29.6%        24.9%        50.0%      |   0.0%         6.7%         0.0%        63.5%      |
|TERMINAL (d)           |  1/44 (2%)    2/8 (25%)    0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      538          485          485       |   ---          648 (T)      ---          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.006 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.282        (e)        P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.004 **   P=0.033 *    P=0.236      P=0.062    |  P=0.008 **   P=0.282        (e)        P=0.209    |
|LOGISTIC REGRESSION    |  P=0.059      P=0.072      P=0.044 *    P=0.002 ** |  P=0.002 **   P=0.282        (e)        P=0.013 *  |
|COCHRAN-ARMITAGE       |  P=0.021 *                                         |  P=0.055                                           |
|FISHER EXACT           |               P=0.105      P=0.059      P=0.016 *  |               P=0.423        (e)        P=0.122    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    4/45 (9%)    7/74 (9%)    8/60 (13%) |  0/60 (0%)    1/44 (2%)    0/75 (0%)    3/60 (5%)  |
|ADJUSTED (b)           |   2.3%        29.6%        24.9%        50.0%      |   0.0%         6.7%         0.0%        63.5%      |
|TERMINAL (d)           |  1/44 (2%)    2/8 (25%)    0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      538          485          485       |   ---          648 (T)      ---          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.006 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.282        (e)        P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.004 **   P=0.033 *    P=0.236      P=0.062    |  P=0.008 **   P=0.282        (e)        P=0.209    |
|LOGISTIC REGRESSION    |  P=0.059      P=0.072      P=0.044 *    P=0.002 ** |  P=0.002 **   P=0.282        (e)        P=0.013 *  |
|COCHRAN-ARMITAGE       |  P=0.021 *                                         |  P=0.055                                           |
|FISHER EXACT           |               P=0.105      P=0.059      P=0.016 *  |               P=0.423        (e)        P=0.122    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  10
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/44 (0%)    2/75 (3%)    1/60 (2%)  |  0/60 (0%)    1/45 (2%)    1/75 (1%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         7.2%         3.8%      |   0.0%         6.7%         2.2%         5.6%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          555          525       |   ---          648 (T)      436          483       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.040 *      (e)        P=0.107      P=0.344    |  P=0.060      P=0.282      P=0.446      P=0.265    |
|INCIDENTAL TUMOR       |  P=0.379        (e)        P=0.579      P=0.912    |  P=0.392      P=0.282      P=0.897      P=0.887    |
|LOGISTIC REGRESSION    |  P=0.219        (e)        P=0.277      P=0.568    |  P=0.369      P=0.282      P=0.858      P=0.694    |
|COCHRAN-ARMITAGE       |  P=0.256                                           |  P=0.409                                           |
|FISHER EXACT           |                 (e)        P=0.307      P=0.500    |               P=0.429      P=0.556      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         6.7%         0.0%        35.1%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          648 (T)      ---          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.002 **   P=0.282        (e)        P=0.026 *  |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.043 *    P=0.282        (e)        P=0.424    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.034 *    P=0.282        (e)        P=0.184    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.160                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.429        (e)        P=0.248    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  11
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |  1/60 (2%)    2/45 (4%)   14/75 (19%)  20/60 (33%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   2.2%         6.7%        57.5%        88.5%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  1/45 (2%)    0/15 (0%)    2/6 (33%)    0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   648 (T)      512          333          284       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.252      P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.559      P=0.007 **   P=0.008 ** |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.469      P=0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |    (e)                                             |  P<0.001 **                                        |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.393      P=0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |  1/60 (2%)    3/45 (7%)   14/75 (19%)  21/60 (35%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   2.2%        12.9%        57.5%        88.8%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  1/45 (2%)    1/15 (7%)    2/6 (33%)    0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   648 (T)      512          333          284       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.078      P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.239      P=0.007 **   P=0.006 ** |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.210      P=0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |    (e)                                             |  P<0.001 **                                        |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.209      P=0.001 **   P<0.001 ** |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  12
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/45 (0%)    2/75 (3%)    0/60 (0%)  | 14/60 (23%)  11/45 (24%)   9/75 (12%)   4/60 (7%)  |
|ADJUSTED (b)           |   2.3%         0.0%         6.1%         0.0%      |  29.3%        50.7%        57.1%        56.4%      |
|TERMINAL (d)           |  1/44 (2%)    0/8 (0%)     0/0          0/0        | 12/45 (27%)   6/15 (40%)   2/6 (33%)    0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      ---          486          ---       |   532          424          476          344       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.373      P=0.831N     P=0.140        (e)      |  P<0.001 **   P=0.038 *    P=0.003 **   P=0.006 ** |
|INCIDENTAL TUMOR       |  P=0.577N     P=0.831N     P=0.662        (e)      |  P=0.450N     P=0.256      P=0.454      P=0.429N   |
|LOGISTIC REGRESSION    |  P=0.519N     P=0.831N     P=0.592        (e)      |  P=0.503      P=0.383      P=0.248      P=0.525N   |
|COCHRAN-ARMITAGE       |  P=0.439N                                          |  P=0.003N**                                        |
|FISHER EXACT           |               P=0.571N     P=0.584      P=0.500N   |               P=0.537      P=0.066N     P=0.010N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/45 (0%)    2/75 (3%)    0/60 (0%)  | 14/60 (23%)  11/45 (24%)   9/75 (12%)   6/60 (10%) |
|ADJUSTED (b)           |   2.3%         0.0%         6.1%         0.0%      |  29.3%        50.7%        57.1%        71.7%      |
|TERMINAL (d)           |  1/44 (2%)    0/8 (0%)     0/0          0/0        | 12/45 (27%)   6/15 (40%)   2/6 (33%)    0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      ---          486          ---       |   532          424          476          344       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.373      P=0.831N     P=0.140        (e)      |  P<0.001 **   P=0.038 *    P=0.003 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.577N     P=0.831N     P=0.662        (e)      |  P=0.426      P=0.256      P=0.454      P=0.672N   |
|LOGISTIC REGRESSION    |  P=0.519N     P=0.831N     P=0.592        (e)      |  P=0.252      P=0.383      P=0.248      P=0.553    |
|COCHRAN-ARMITAGE       |  P=0.439N                                          |  P=0.013N*                                         |
|FISHER EXACT           |               P=0.571N     P=0.584      P=0.500N   |               P=0.537      P=0.066N     P=0.042N*  |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  13
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/45 (0%)    2/75 (3%)    0/60 (0%)  | 15/60 (25%)  13/45 (29%)  21/75 (28%)  22/60 (37%) |
|ADJUSTED (b)           |   2.3%         0.0%         6.1%         0.0%      |  31.4%        54.0%        78.9%        89.5%      |
|TERMINAL (d)           |  1/44 (2%)    0/8 (0%)     0/0          0/0        | 13/45 (29%)   6/15 (40%)   3/6 (50%)    0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      ---          486          ---       |   532          424          333          284       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.373      P=0.831N     P=0.140        (e)      |  P<0.001 **   P=0.016 *    P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.577N     P=0.831N     P=0.662        (e)      |  P=0.005 **   P=0.207      P=0.073      P=0.070    |
|LOGISTIC REGRESSION    |  P=0.519N     P=0.831N     P=0.592        (e)      |  P=0.001 **   P=0.294      P=0.024 *    P=0.030 *  |
|COCHRAN-ARMITAGE       |  P=0.439N                                          |  P=0.101                                           |
|FISHER EXACT           |               P=0.571N     P=0.584      P=0.500N   |               P=0.410      P=0.424      P=0.118    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery                                                                                                                        |
|     Schwannoma Malignant                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|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%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         3.1%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          420          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.542        (e)        P=0.259        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.421N       (e)        P=0.769        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.632N       (e)        P=0.387        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.595                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.307        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  14
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    7/45 (16%)  10/75 (13%)   9/60 (15%) |  2/60 (3%)    2/45 (4%)    3/75 (4%)    3/60 (5%)  |
|ADJUSTED (b)           |   2.3%        41.9%        50.4%       100.0%      |   4.4%        12.5%        21.6%        63.5%      |
|TERMINAL (d)           |  1/44 (2%)    2/8 (25%)    0/0          0/0        |  2/45 (4%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      485          333          402       |   648 (T)      644          450          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.283      P=0.040 *    P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.064      P=0.019 *    P=0.170      P=0.081    |  P=0.109      P=0.447      P=0.440      P=0.209    |
|LOGISTIC REGRESSION    |  P=0.015 *    P=0.009 **   P=0.028 *    P=0.007 ** |  P=0.018 *    P=0.306      P=0.257      P=0.062    |
|COCHRAN-ARMITAGE       |  P=0.034 *                                         |  P=0.422                                           |
|FISHER EXACT           |               P=0.011 *    P=0.012 *    P=0.008 ** |               P=0.576      P=0.605      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/45 (2%)    0/75 (0%)    2/60 (3%)  |  0/60 (0%)    0/45 (0%)    3/75 (4%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%         4.2%         0.0%         5.7%      |   0.0%         0.0%         7.0%        10.3%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          602          ---          401       |   ---          ---          331          431       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.022 *    P=0.342        (e)        P=0.148    |  P=0.016 *      (e)        P=0.078      P=0.055    |
|INCIDENTAL TUMOR       |  P=0.373      P=0.741        (e)        P=0.769    |  P=0.512        (e)        P=0.744      P=0.730    |
|LOGISTIC REGRESSION    |  P=0.218      P=0.441        (e)        P=0.380    |  P=0.339        (e)        P=0.527      P=0.429    |
|COCHRAN-ARMITAGE       |  P=0.160                                           |  P=0.105                                           |
|FISHER EXACT           |               P=0.429        (e)        P=0.248    |                 (e)        P=0.168      P=0.248    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  15
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    8/45 (18%)  10/75 (13%)  11/60 (18%) |  2/60 (3%)    2/45 (4%)    6/75 (8%)    5/60 (8%)  |
|ADJUSTED (b)           |   2.3%        44.3%        50.4%       100.0%      |   4.4%        12.5%        27.1%        67.3%      |
|TERMINAL (d)           |  1/44 (2%)    2/8 (25%)    0/0          0/0        |  2/45 (4%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      485          333          401       |   648 (T)      644          331          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.283      P=0.004 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.042 *    P=0.015 *    P=0.170      P=0.068    |  P=0.116      P=0.447      P=0.359      P=0.167    |
|LOGISTIC REGRESSION    |  P=0.007 **   P=0.004 **   P=0.028 *    P=0.004 ** |  P=0.028 *    P=0.306      P=0.212      P=0.028 *  |
|COCHRAN-ARMITAGE       |  P=0.014 *                                         |  P=0.141                                           |
|FISHER EXACT           |               P=0.005 **   P=0.012 *    P=0.002 ** |               P=0.576      P=0.222      P=0.219    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/44 (5%)    0/75 (0%)    1/60 (2%)  |  0/60 (0%)    0/43 (0%)    0/75 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%        15.9%         0.0%       100.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    1/8 (13%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          596          ---          597       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.043 *      (e)        P<0.001 ** |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.272      P=0.150        (e)        P=0.638    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.103      P=0.122        (e)        P=0.281    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.581                                           |    (e)                                             |
|FISHER EXACT           |               P=0.177        (e)        P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  16
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pharynx                                                                                                                          |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    4/45 (9%)    5/75 (7%)    3/60 (5%)  |  1/60 (2%)    0/45 (0%)    3/75 (4%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%        26.3%        32.8%        40.4%      |   2.2%         0.0%        21.6%         2.6%      |
|TERMINAL (d)           |  0/44 (0%)    1/8 (13%)    0/0          0/0        |  1/45 (2%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          556          408          476       |   648 (T)      ---          450          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.002 **   P=0.004 **   P=0.003 ** |  P=0.027 *    P=0.718N     P=0.021 *    P=0.412    |
|INCIDENTAL TUMOR       |  P=0.399      P=0.096      P=0.403      P=0.356    |  P=0.455      P=0.718N     P=0.379      P=0.887    |
|LOGISTIC REGRESSION    |  P=0.157      P=0.023 *    P=0.098      P=0.092    |  P=0.341      P=0.718N     P=0.158      P=0.884N   |
|COCHRAN-ARMITAGE       |  P=0.253                                           |  P=0.490                                           |
|FISHER EXACT           |               P=0.031 *    P=0.050 *    P=0.122    |               P=0.571N     P=0.398      P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/58 (3%)    1/43 (2%)    0/74 (0%)    3/59 (5%)  | 15/60 (25%)   9/45 (20%)   5/75 (7%)    8/60 (13%) |
|ADJUSTED (b)           |   4.1%        12.5%         0.0%         7.4%      |  29.5%        37.2%        40.4%        70.4%      |
|TERMINAL (d)           |  1/44 (2%)    1/8 (13%)    0/0          0/0        | 10/45 (22%)   3/15 (20%)   2/6 (33%)    0/0        |
|FIRST INCIDENCE (DAYS) |   581          647 (T)      ---          423       |   574          505          468          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.013 *    P=0.594      P=0.767N     P=0.091    |  P<0.001 **   P=0.212      P=0.190      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.271      P=0.733N     P=0.196N     P=0.527N   |  P=0.558N     P=0.336N     P=0.176N     P=0.407N   |
|LOGISTIC REGRESSION    |  P=0.389      P=0.691N     P=0.344N     P=0.673    |  P=0.242      P=0.528N     P=0.375N     P=0.388    |
|COCHRAN-ARMITAGE       |  P=0.393                                           |  P=0.030N*                                         |
|FISHER EXACT           |               P=0.612N     P=0.191N     P=0.508    |               P=0.358N     P=0.003N**   P=0.082N   |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  17
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/58 (0%)    0/43 (0%)    0/74 (0%)    0/59 (0%)  |  2/60 (3%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.1%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  1/45 (2%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   600          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.462N     P=0.443N     P=0.674N     P=0.952N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.223N     P=0.277N     P=0.341N     P=0.500N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.297N     P=0.333N     P=0.484N     P=0.730N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.098N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.324N     P=0.196N     P=0.248N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/58 (3%)    1/43 (2%)    0/74 (0%)    3/59 (5%)  | 17/60 (28%)   9/45 (20%)   5/75 (7%)    8/60 (13%) |
|ADJUSTED (b)           |   4.1%        12.5%         0.0%         7.4%      |  32.8%        37.2%        40.4%        70.4%      |
|TERMINAL (d)           |  1/44 (2%)    1/8 (13%)    0/0          0/0        | 11/45 (24%)   3/15 (20%)   2/6 (33%)    0/0        |
|FIRST INCIDENCE (DAYS) |   581          647 (T)      ---          423       |   574          505          468          408       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.013 *    P=0.594      P=0.767N     P=0.091    |  P<0.001 **   P=0.309      P=0.252      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.271      P=0.733N     P=0.196N     P=0.527N   |  P=0.420N     P=0.195N     P=0.086N     P=0.275N   |
|LOGISTIC REGRESSION    |  P=0.389      P=0.691N     P=0.344N     P=0.673    |  P=0.351      P=0.375N     P=0.255N     P=0.497    |
|COCHRAN-ARMITAGE       |  P=0.393                                           |  P=0.011N*                                         |
|FISHER EXACT           |               P=0.612N     P=0.191N     P=0.508    |               P=0.227N     P<0.001N**   P=0.035N*  |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  18
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Salivary Glands                                                                                                                  |
|     Schwannoma Malignant                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/44 (5%)    0/75 (0%)    0/60 (0%)  |  0/59 (0%)    0/44 (0%)    1/75 (1%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%        13.5%         0.0%         0.0%      |   0.0%         0.0%         4.2%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/44 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          596          ---          ---       |   ---          ---          550          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.413      P=0.049 *      (e)          (e)      |  P=0.465        (e)        P=0.331        (e)      |
|INCIDENTAL TUMOR       |  P=0.308N     P=0.529        (e)          (e)      |  P=0.674        (e)        P=0.598        (e)      |
|LOGISTIC REGRESSION    |  P=0.752      P=0.127        (e)          (e)      |  P=0.672        (e)        P=0.526        (e)      |
|COCHRAN-ARMITAGE       |  P=0.359N                                          |  P=0.692                                           |
|FISHER EXACT           |               P=0.177        (e)          (e)      |                 (e)        P=0.560        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)   31/45 (69%)  47/75 (63%)  35/60 (58%) |  0/60 (0%)    3/45 (7%)    3/75 (4%)    2/60 (3%)  |
|ADJUSTED (b)           |   2.3%        96.5%       100.0%       100.0%      |   0.0%        20.0%        24.5%        66.7%      |
|TERMINAL (d)           |  1/44 (2%)    7/8 (88%)    0/0          0/0        |  0/45 (0%)    3/15 (20%)   0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      480          424          419       |   ---          648 (T)      423          610       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.009 **   P=0.006 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.035 *    P=0.009 **   P=0.311      P=0.234    |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.003 **   P=0.009 **   P=0.058      P=0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.356                                           |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P=0.076      P=0.168      P=0.248    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  19
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Carcinoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    4/45 (9%)   18/75 (24%)  17/60 (28%) |  0/60 (0%)    1/45 (2%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   2.3%        16.9%        47.8%        73.3%      |   0.0%         6.7%         0.0%         0.0%      |
|TERMINAL (d)           |  1/44 (2%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      552          417          344       |   ---          648 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.016 *    P<0.001 **   P<0.001 ** |  P=0.732      P=0.282        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.009 **   P=0.384      P=0.066      P=0.027 *  |  P=0.732      P=0.282        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.014 *    P=0.092      P<0.001 **   P<0.001 ** |  P=0.732      P=0.282        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.531N                                          |
|FISHER EXACT           |               P=0.105      P<0.001 **   P<0.001 ** |               P=0.429        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    5/45 (11%)   7/75 (9%)    1/60 (2%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   1.8%        30.6%        37.0%         5.6%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   573          556          391          546       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006 **   P=0.003 **   P=0.002 **   P=0.370    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.105N     P=0.554      P=0.594      P=0.451N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.572N     P=0.041 *    P=0.103      P=0.814    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.403N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.051      P=0.061      P=0.752N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  20
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    9/45 (20%)  24/75 (32%)  21/60 (35%) |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        48.8%        90.8%       100.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    2/8 (25%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          485          424          445       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.006 **   P=0.006 **   P=0.001 ** |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |    (e)                                             |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)   13/45 (29%)  28/75 (37%)  22/60 (37%) |  0/60 (0%)    0/45 (0%)    3/75 (4%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        62.0%        91.7%       100.0%      |   0.0%         0.0%        20.4%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    3/8 (38%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          485          424          445       |   ---          ---          361          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.117        (e)        P=0.014 *      (e)      |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P=0.004 **   P<0.001 ** |  P=0.640N       (e)        P=0.351        (e)      |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.547        (e)        P=0.126        (e)      |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.542                                           |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |                 (e)        P=0.168        (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  21
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    5/45 (11%)   7/75 (9%)    5/60 (8%)  |  0/60 (0%)    0/45 (0%)    3/75 (4%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        33.1%        43.7%        33.1%      |   0.0%         0.0%        20.4%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    2/8 (25%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          515          525          445       |   ---          ---          361          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.117        (e)        P=0.014 *      (e)      |
|INCIDENTAL TUMOR       |  P=0.250      P=0.010 **   P=0.294      P=0.216    |  P=0.640N       (e)        P=0.351        (e)      |
|LOGISTIC REGRESSION    |  P=0.016 *    P=0.015 *    P=0.004 **   P=0.031 *  |  P=0.547        (e)        P=0.126        (e)      |
|COCHRAN-ARMITAGE       |  P=0.107                                           |  P=0.542                                           |
|FISHER EXACT           |               P=0.013 *    P=0.014 *    P=0.029 *  |                 (e)        P=0.168        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)   32/45 (71%)  54/75 (72%)  40/60 (67%) |  0/60 (0%)    4/45 (9%)    3/75 (4%)    2/60 (3%)  |
|ADJUSTED (b)           |   4.5%        96.6%       100.0%       100.0%      |   0.0%        26.7%        24.5%        66.7%      |
|TERMINAL (d)           |  2/44 (5%)    7/8 (88%)    0/0          0/0        |  0/45 (0%)    4/15 (27%)   0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      480          417          344       |   ---          648 (T)      423          610       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.002 **   P=0.006 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.025 *    P=0.002 **   P=0.311      P=0.234    |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.003 **   P=0.002 **   P=0.058      P=0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.440                                           |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P=0.031 *    P=0.168      P=0.248    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  22
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)   35/45 (78%)  57/75 (76%)  43/60 (72%) |  0/60 (0%)    4/45 (9%)    5/75 (7%)    2/60 (3%)  |
|ADJUSTED (b)           |   6.3%       100.0%       100.0%       100.0%      |   0.0%        26.7%        29.9%        66.7%      |
|TERMINAL (d)           |  2/44 (5%)    8/8 (100%)   0/0          0/0        |  0/45 (0%)    4/15 (27%)   0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   573          480          391          344       |   ---          648 (T)      361          610       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.057      P=0.002 **   P=0.195      P=0.234    |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.018 *    P=0.002 **   P=0.031 *    P=0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.407                                           |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P=0.031 *    P=0.050 *    P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Sebaceous Gland                                                                                                            |
|     Carcinoma, Basal Cell Carcinoma or Adenoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/45 (4%)    3/75 (4%)    2/60 (3%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        14.5%         5.8%         5.1%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    1/8 (13%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          353          472          337       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.063      P=0.067      P=0.106      P=0.166    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.618N     P=0.145      P=0.661      P=0.734    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.509      P=0.210      P=0.253      P=0.397    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.268                                           |    (e)                                             |
|FISHER EXACT           |               P=0.181      P=0.168      P=0.248    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  23
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    4/45 (9%)    4/75 (5%)    2/60 (3%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        17.6%        22.5%       100.0%      |   0.0%         6.7%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          546          556          483       |   ---          648 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002 **   P=0.009 **   P=0.003 **   P=0.016 *  |  P=0.732      P=0.282        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.563N     P=0.260      P=0.356      P=0.549    |  P=0.732      P=0.282        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.223      P=0.041 *    P=0.043 *    P=0.227    |  P=0.732      P=0.282        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.422                                           |  P=0.531N                                          |
|FISHER EXACT           |               P=0.031 *    P=0.092      P=0.248    |               P=0.429        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibroma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/45 (4%)    2/75 (3%)    2/60 (3%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        18.2%       100.0%         9.7%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          641          358          424       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.018 *    P=0.036 *    P=0.083    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.465      P=0.529      P=0.600      P=0.549    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.257      P=0.033 *    P=0.384      P=0.353    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.274                                           |    (e)                                             |
|FISHER EXACT           |               P=0.181      P=0.307      P=0.248    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  24
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibroma or Fibroma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    6/45 (13%)   6/75 (8%)    4/60 (7%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        33.5%       100.0%       100.0%      |   0.0%         6.7%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          546          358          424       |   ---          648 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.001 ** |  P=0.732      P=0.282        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.510      P=0.158      P=0.242      P=0.320    |  P=0.732      P=0.282        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.115      P=0.006 **   P=0.032 *    P=0.093    |  P=0.732      P=0.282        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.241                                           |  P=0.531N                                          |
|FISHER EXACT           |               P=0.005 **   P=0.027 *    P=0.059    |               P=0.429        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    6/45 (13%)   6/75 (8%)    5/60 (8%)  |  0/60 (0%)    1/45 (2%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.9%        33.5%       100.0%       100.0%      |   0.0%         6.7%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   452          546          358          424       |   ---          648 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.004 **   P=0.002 **   P=0.006 ** |  P=0.732      P=0.282        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.531N     P=0.367      P=0.606      P=0.695    |  P=0.732      P=0.282        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.242      P=0.075      P=0.267      P=0.353    |  P=0.732      P=0.282        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.341                                           |  P=0.531N                                          |
|FISHER EXACT           |               P=0.062      P=0.222      P=0.219    |               P=0.429        (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  25
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/45 (0%)    0/75 (0%)    1/60 (2%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.9%         0.0%         0.0%         2.9%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   452          ---          ---          485       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.558      P=0.456N     P=0.490N     P=0.661    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.393N     P=0.388N     P=0.088N     P=0.231N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.345N     P=0.265N     P=0.131N     P=0.390N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.421N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.324N     P=0.196N     P=0.500N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.9%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   452          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.292N     P=0.456N     P=0.490N     P=0.573N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.077N     P=0.388N     P=0.088N     P=0.088N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.066N     P=0.265N     P=0.131N     P=0.167N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.098N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.324N     P=0.196N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  26
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 57/60 (95%)  39/45 (87%)  68/75 (91%)  42/59 (71%) |                                                    |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |                                                    |
|TERMINAL (d)           | 44/44 (100%)  8/8 (100%)   0/0          0/0        |                                                    |
|FIRST INCIDENCE (DAYS) |   529          480          333          344       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |                                                    |
|INCIDENTAL TUMOR       |  P=0.329N     P=0.520      P=0.054      P=0.465    |                                                    |
|LOGISTIC REGRESSION    |  P=0.530N     P=0.675      P=0.007 **   P=0.439    |                                                    |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |                                                    |
|FISHER EXACT           |               P=0.124N     P=0.270N     P<0.001N** |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/60 (10%)   6/44 (14%)   5/74 (7%)    1/60 (2%)  |  4/60 (7%)    1/44 (2%)    2/75 (3%)    1/59 (2%)  |
|ADJUSTED (b)           |  13.2%        34.9%        27.4%        33.3%      |   8.0%         4.0%        33.3%         4.0%      |
|TERMINAL (d)           |  5/44 (11%)   1/8 (13%)    0/0          0/0        |  2/45 (4%)    0/15 (0%)    2/6 (33%)    0/0        |
|FIRST INCIDENCE (DAYS) |   645          578          538          592       |   543          616          648 (T)      436       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.011 *    P<0.001 **   P=0.024 *  |  P=0.094      P=0.514N     P=0.235      P=0.472    |
|INCIDENTAL TUMOR       |  P=0.362N     P=0.277      P=0.321      P=0.638    |  P=0.484N     P=0.166N     P=0.715      P=0.124N   |
|LOGISTIC REGRESSION    |  P=0.450      P=0.161      P=0.283      P=0.474    |  P=0.589      P=0.288N     P=0.497      P=0.410N   |
|COCHRAN-ARMITAGE       |  P=0.025N*                                         |  P=0.136N                                          |
|FISHER EXACT           |               P=0.392      P=0.356N     P=0.057N   |               P=0.293N     P=0.241N     P=0.187N   |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  27
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/44 (2%)    2/74 (3%)    1/60 (2%)  |  1/60 (2%)    0/44 (0%)    1/75 (1%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%         8.3%        50.7%         8.3%      |   1.9%         0.0%        11.1%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          638          358          560       |   599          ---          616          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.010 **   P=0.223      P=0.044 *    P=0.201    |  P=0.531      P=0.620N     P=0.356      P=0.954N   |
|INCIDENTAL TUMOR       |  P=0.517      P=0.741      P=0.600      P=0.638    |  P=0.426N     P=0.391N     P=0.649N     P=0.500N   |
|LOGISTIC REGRESSION    |  P=0.363      P=0.305      P=0.381      P=0.479    |  P=0.755      P=0.536N     P=0.619      P=0.820N   |
|COCHRAN-ARMITAGE       |  P=0.391                                           |  P=0.384N                                          |
|FISHER EXACT           |               P=0.423      P=0.303      P=0.500    |               P=0.577N     P=0.693N     P=0.504N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/60 (10%)   7/44 (16%)   7/74 (9%)    2/60 (3%)  |  5/60 (8%)    1/44 (2%)    3/75 (4%)    1/59 (2%)  |
|ADJUSTED (b)           |  13.2%        40.3%        64.2%        38.9%      |   9.8%         4.0%        40.7%         4.0%      |
|TERMINAL (d)           |  5/44 (11%)   1/8 (13%)    0/0          0/0        |  2/45 (4%)    0/15 (0%)    2/6 (33%)    0/0        |
|FIRST INCIDENCE (DAYS) |   645          578          358          560       |   543          616          616          436       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.003 **   P<0.001 **   P=0.002 ** |  P=0.066      P=0.388N     P=0.094      P=0.518    |
|INCIDENTAL TUMOR       |  P=0.454N     P=0.227      P=0.221      P=0.399    |  P=0.336N     P=0.072N     P=0.602N     P=0.061N   |
|LOGISTIC REGRESSION    |  P=0.389      P=0.075      P=0.288      P=0.254    |  P=0.580      P=0.176N     P=0.369      P=0.276N   |
|COCHRAN-ARMITAGE       |  P=0.064N                                          |  P=0.091N                                          |
|FISHER EXACT           |               P=0.272      P=0.571N     P=0.136N   |               P=0.191N     P=0.243N     P=0.107N   |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  28
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/44 (2%)    0/74 (0%)    0/60 (0%)  |  2/60 (3%)    1/44 (2%)    0/75 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%         5.0%         0.0%         0.0%      |   4.4%         6.7%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  2/45 (4%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          606          ---          ---       |   648 (T)      648 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.748      P=0.314        (e)          (e)      |  P=0.738N     P=0.633      P=0.721N       (e)      |
|INCIDENTAL TUMOR       |  P=0.518N     P=0.741        (e)          (e)      |  P=0.738N     P=0.633      P=0.721N       (e)      |
|LOGISTIC REGRESSION    |  P=0.802N     P=0.432        (e)          (e)      |  P=0.738N     P=0.633      P=0.721N       (e)      |
|COCHRAN-ARMITAGE       |  P=0.530N                                          |  P=0.082N                                          |
|FISHER EXACT           |               P=0.423        (e)          (e)      |               P=0.616N     P=0.196N     P=0.252N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/44 (2%)    0/74 (0%)    1/60 (2%)  |  2/60 (3%)    1/44 (2%)    1/75 (1%)    1/59 (2%)  |
|ADJUSTED (b)           |   0.0%         5.0%         0.0%        20.0%      |   4.4%         6.7%         9.1%        14.3%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  2/45 (4%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          606          ---          585       |   648 (T)      648 (T)      597          563       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.012 *    P=0.314        (e)        P=0.070    |  P=0.036 *    P=0.633      P=0.437      P=0.108    |
|INCIDENTAL TUMOR       |  P=0.445      P=0.741        (e)        P=0.638    |  P=0.249      P=0.633      P=0.704      P=0.500    |
|LOGISTIC REGRESSION    |  P=0.165      P=0.432        (e)        P=0.360    |  P=0.207      P=0.633      P=0.615      P=0.501    |
|COCHRAN-ARMITAGE       |  P=0.435                                           |  P=0.368N                                          |
|FISHER EXACT           |               P=0.423        (e)        P=0.500    |               P=0.616N     P=0.416N     P=0.506N   |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  29
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tongue                                                                                                                           |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/45 (2%)    0/75 (0%)    1/60 (2%)  |  0/60 (0%)    0/45 (0%)    2/75 (3%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%         4.2%         0.0%         1.9%      |   0.0%         0.0%         5.6%        10.3%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          602          ---          401       |   ---          ---          423          431       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.145      P=0.342        (e)        P=0.479    |  P=0.010 *      (e)        P=0.142      P=0.055    |
|INCIDENTAL TUMOR       |  P=0.636      P=0.741        (e)        P=0.912    |  P=0.360        (e)        P=0.744      P=0.730    |
|LOGISTIC REGRESSION    |  P=0.535      P=0.441        (e)        P=0.631    |  P=0.176        (e)        P=0.497      P=0.429    |
|COCHRAN-ARMITAGE       |  P=0.433                                           |  P=0.094                                           |
|FISHER EXACT           |               P=0.429        (e)        P=0.500    |                 (e)        P=0.307      P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tongue                                                                                                                           |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    4/45 (9%)    5/75 (7%)    8/60 (13%) |  1/60 (2%)    2/45 (4%)    2/75 (3%)    4/60 (7%)  |
|ADJUSTED (b)           |   2.3%        22.8%        26.2%       100.0%      |   2.2%        12.5%         5.6%        66.4%      |
|TERMINAL (d)           |  1/44 (2%)    1/8 (13%)    0/0          0/0        |  1/45 (2%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      485          333          401       |   648 (T)      644          423          431       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.010 **   P=0.002 **   P<0.001 ** |  P<0.001 **   P=0.161      P=0.209      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.028 *    P=0.133      P=0.335      P=0.122    |  P=0.077      P=0.318      P=0.771      P=0.187    |
|LOGISTIC REGRESSION    |  P=0.015 *    P=0.103      P=0.185      P=0.027 *  |  P=0.011 *    P=0.178      P=0.677      P=0.012 *  |
|COCHRAN-ARMITAGE       |  P=0.020 *                                         |  P=0.141                                           |
|FISHER EXACT           |               P=0.105      P=0.165      P=0.016 *  |               P=0.393      P=0.584      P=0.182    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  30
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tongue                                                                                                                           |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    3/45 (7%)    5/75 (7%)    7/60 (12%) |  1/60 (2%)    2/45 (4%)    0/75 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   2.3%        19.5%        26.2%       100.0%      |   2.2%        12.5%         0.0%        62.5%      |
|TERMINAL (d)           |  1/44 (2%)    1/8 (13%)    0/0          0/0        |  1/45 (2%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   647 (T)      485          333          402       |   648 (T)      644          ---          602       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.033 *    P=0.002 **   P<0.001 ** |  P<0.001 **   P=0.161      P=0.882N     P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.026 *    P=0.168      P=0.335      P=0.133    |  P=0.101      P=0.318      P=0.882N     P=0.234    |
|LOGISTIC REGRESSION    |  P=0.014 *    P=0.212      P=0.185      P=0.023 *  |  P=0.003 **   P=0.178      P=0.882N     P=0.008 ** |
|COCHRAN-ARMITAGE       |  P=0.026 *                                         |  P=0.519                                           |
|FISHER EXACT           |               P=0.209      P=0.165      P=0.031 *  |               P=0.393      P=0.444N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/60 (0%)    3/45 (7%)    1/75 (1%)    2/60 (3%)  |
|ADJUSTED (b)           |                                                    |   0.0%        16.5%        16.7%        57.1%      |
|TERMINAL (d)           |                                                    |  0/45 (0%)    1/15 (7%)    1/6 (17%)    0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          618          648 (T)      563       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P<0.001 **   P=0.014 *    P=0.118      P<0.001 ** |
|INCIDENTAL TUMOR       |                                                    |  P=0.052      P=0.109      P=0.118      P=0.234    |
|LOGISTIC REGRESSION    |                                                    |  P=0.001 **   P=0.029 *    P=0.118      P=0.010 ** |
|COCHRAN-ARMITAGE       |                                                    |  P=0.385                                           |
|FISHER EXACT           |                                                    |               P=0.076      P=0.556      P=0.248    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  31
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  6/60 (10%)   8/45 (18%)   7/75 (9%)    5/60 (8%)  |
|ADJUSTED (b)           |                                                    |  13.3%        30.3%        24.0%        32.5%      |
|TERMINAL (d)           |                                                    |  6/45 (13%)   2/15 (13%)   0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   648 (T)      436          424          378       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P<0.001 **   P=0.020 *    P=0.009 **   P<0.001 ** |
|INCIDENTAL TUMOR       |                                                    |  P=0.554N     P=0.187      P=0.386      P=0.167    |
|LOGISTIC REGRESSION    |                                                    |  P=0.445      P=0.214      P=0.397      P=0.240    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.271N                                          |
|FISHER EXACT           |                                                    |               P=0.192      P=0.561N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/60 (2%)    1/45 (2%)    2/75 (3%)    1/60 (2%)  |
|ADJUSTED (b)           |                                                    |   2.2%         6.7%         3.0%         4.5%      |
|TERMINAL (d)           |                                                    |  1/45 (2%)    1/15 (7%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   648 (T)      648 (T)      309          450       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.161      P=0.500      P=0.331      P=0.304    |
|INCIDENTAL TUMOR       |                                                    |  P=0.618N     P=0.500      P=0.882N     P=0.887    |
|LOGISTIC REGRESSION    |                                                    |  P=0.419N     P=0.500      P=0.560N     P=0.819    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.613N                                          |
|FISHER EXACT           |                                                    |               P=0.676      P=0.584      P=0.752N   |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  32
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  7/60 (12%)   9/45 (20%)   9/75 (12%)   6/60 (10%) |
|ADJUSTED (b)           |                                                    |  15.6%        35.7%        26.3%        35.6%      |
|TERMINAL (d)           |                                                    |  7/45 (16%)   3/15 (20%)   0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   648 (T)      436          309          378       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P<0.001 **   P=0.012 *    P=0.004 **   P<0.001 ** |
|INCIDENTAL TUMOR       |                                                    |  P=0.527N     P=0.126      P=0.424      P=0.149    |
|LOGISTIC REGRESSION    |                                                    |  P=0.567      P=0.170      P=0.576      P=0.218    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.285N                                          |
|FISHER EXACT           |                                                    |               P=0.183      P=0.585      P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    4/45 (9%)   11/75 (15%)   9/60 (15%) |  0/60 (0%)    3/45 (7%)    4/75 (5%)    3/60 (5%)  |
|ADJUSTED (b)           |   0.0%        18.9%       100.0%        62.5%      |   0.0%        11.2%        14.4%        26.7%      |
|TERMINAL (d)           |  0/44 (0%)    1/8 (13%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   ---          353          391          445       |   ---          424          424          424       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.011 *    P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.036 *    P=0.010 **   P=0.005 ** |
|INCIDENTAL TUMOR       |  P=0.069      P=0.081      P=0.163      P=0.081    |  P=0.408      P=0.267      P=0.277      P=0.366    |
|LOGISTIC REGRESSION    |  P=0.006 **   P=0.049 *    P=0.004 **   P<0.001 ** |  P=0.368      P=0.150      P=0.090      P=0.071    |
|COCHRAN-ARMITAGE       |  P=0.005 **                                        |  P=0.195                                           |
|FISHER EXACT           |               P=0.031 *    P=0.001 **   P=0.001 ** |               P=0.076      P=0.092      P=0.122    |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  33
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    7/45 (16%)  14/75 (19%)  21/60 (35%) |  1/60 (2%)   10/45 (22%)  17/75 (23%)  13/60 (22%) |
|ADJUSTED (b)           |   0.0%        20.1%        67.3%       100.0%      |   1.7%        28.4%        53.8%        51.2%      |
|TERMINAL (d)           |  0/44 (0%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    1/6 (17%)    0/0        |
|FIRST INCIDENCE (DAYS) |   ---          262          304          284       |   402          424          274          262       |
|-----------------------|                                                    |                                                    |
|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=0.019 *    P=0.063      P=0.128      P=0.017 *  |  P=0.422      P=0.061      P=0.041 *    P=0.488    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.006 **   P=0.004 **   P<0.001 ** |  P=0.489      P=0.014 *    P=0.011 *    P=0.145    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.007 **                                        |
|FISHER EXACT           |               P=0.002 **   P<0.001 **   P<0.001 ** |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)   10/45 (22%)  25/75 (33%)  30/60 (50%) |  1/60 (2%)   12/45 (27%)  21/75 (28%)  16/60 (27%) |
|ADJUSTED (b)           |   0.0%        33.7%       100.0%       100.0%      |   1.7%        33.4%        60.5%        64.5%      |
|TERMINAL (d)           |  0/44 (0%)    1/8 (13%)    0/0          0/0        |  0/45 (0%)    0/15 (0%)    1/6 (17%)    0/0        |
|FIRST INCIDENCE (DAYS) |   ---          262          304          284       |   402          424          274          262       |
|-----------------------|                                                    |                                                    |
|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=0.008 **   P=0.025 *    P<0.001 ** |  P=0.296      P=0.028 *    P=0.012 *    P=0.250    |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P=0.354      P=0.005 **   P=0.001 **   P=0.019 *  |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.002 **                                        |
|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: 05172 TEST: 01                                                 PAGE  34
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 19/60 (32%)  17/45 (38%)  17/75 (23%)   4/60 (7%)  | 21/60 (35%)  15/45 (33%)  12/75 (16%)   4/60 (7%)  |
|ADJUSTED (b)           |  38.6%        73.9%        83.2%        15.1%      |  39.0%        57.6%        68.4%        58.6%      |
|TERMINAL (d)           | 14/44 (32%)   4/8 (50%)    0/0          0/0        | 13/45 (29%)   6/15 (40%)   3/6 (50%)    0/0        |
|FIRST INCIDENCE (DAYS) |   505          515          483          486       |   532          562          419          430       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.033 *  |  P<0.001 **   P=0.052      P=0.003 **   P=0.019 *  |
|INCIDENTAL TUMOR       |  P=0.043N*    P=0.096      P=0.326      P=0.194N   |  P=0.089N     P=0.460N     P=0.286N     P=0.010N** |
|LOGISTIC REGRESSION    |  P=0.206N     P=0.108      P=0.199      P=0.303N   |  P=0.128N     P=0.488N     P=0.311N     P=0.045N*  |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.327      P=0.164N     P<0.001N** |               P=0.513N     P=0.009N**   P<0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/45 (2%)    7/75 (9%)    6/60 (10%) |  0/60 (0%)    0/45 (0%)    0/75 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   4.0%         2.5%        15.4%        43.8%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/44 (2%)    0/8 (0%)     0/0          0/0        |  0/45 (0%)    0/15 (0%)    0/6 (0%)     0/0        |
|FIRST INCIDENCE (DAYS) |   529          483          339          401       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.720      P=0.016 *    P=0.001 ** |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.415      P=0.540N     P=0.690      P=0.648    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.148      P=0.545N     P=0.297      P=0.226    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.053                                           |    (e)                                             |
|FISHER EXACT           |               P=0.607N     P=0.149      P=0.136    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  35
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 57/60 (95%)  43/45 (96%)  70/75 (93%)  53/60 (88%) | 35/60 (58%)  30/45 (67%)  32/75 (43%)  34/60 (57%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  66.9%        89.8%        90.7%       100.0%      |
|TERMINAL (d)           | 44/44 (100%)  8/8 (100%)   0/0          0/0        | 28/45 (62%)  12/15 (80%)   4/6 (67%)    0/0        |
|FIRST INCIDENCE (DAYS) |   529          353          333          332       |   532          424          333          262       |
|-----------------------|                                                    |                                                    |
|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=0.191      P=0.094      P=0.026 *    P=0.029 *  |  P=0.028 *    P=0.110      P=0.447      P=0.086    |
|LOGISTIC REGRESSION    |  P=0.105      P=0.050 *    P=0.006 **   P=0.003 ** |  P=0.003 **   P=0.132      P=0.210      P=0.012 *  |
|COCHRAN-ARMITAGE       |  P=0.080N                                          |  P=0.264N                                          |
|FISHER EXACT           |               P=0.635      P=0.489N     P=0.161N   |               P=0.253      P=0.051N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 27/60 (45%)  36/45 (80%)  66/75 (88%)  59/60 (98%) | 27/60 (45%)  33/45 (73%)  68/75 (91%)  56/60 (93%) |
|ADJUSTED (b)           |  48.8%        94.1%        97.6%       100.0%      |  47.7%        83.9%        96.5%       100.0%      |
|TERMINAL (d)           | 16/44 (36%)   6/8 (75%)    0/0          0/0        | 16/45 (36%)   9/15 (60%)   4/6 (67%)    0/0        |
|FIRST INCIDENCE (DAYS) |   452          262          284          267       |   402          373          220          262       |
|-----------------------|                                                    |                                                    |
|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=0.018 *    P=0.039 *    P<0.001 ** |  P=0.005 **   P=0.064      P=0.027 *    P=0.241    |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P=0.052      P<0.001 ** |  P=0.002 **   P=0.032 *    P=0.054      P=0.386    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P=0.003 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
         DATE: 09/18/94                     EXPERIMENT: 05172 TEST: 01                                                 PAGE  36
                  STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- 3,3-DIMETHOXYBENZIDINE DIHYDROCHLORID
                                                 TERMINAL SACRIFICE AT 93 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      80 PPM       170 PPM      330 PPM   |   CONTROL      80 PPM       170 PPM      330 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 59/60 (98%)  45/45 (100%) 75/75 (100%) 60/60 (100%)| 48/60 (80%)  43/45 (96%)  73/75 (97%)  57/60 (95%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  81.4%        95.6%       100.0%       100.0%      |
|TERMINAL (d)           | 44/44 (100%)  8/8 (100%)   0/0          0/0        | 34/45 (76%)  13/15 (87%)   6/6 (100%)   0/0        |
|FIRST INCIDENCE (DAYS) |   452          262          284          267       |   402          373          220          262       |
|-----------------------|                                                    |                                                    |
|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=0.120      P=0.282      P=0.186      P=0.128    |  P=0.367      P=0.155      P=0.089      P=0.634    |
|LOGISTIC REGRESSION    |  P=0.120      P=0.282      P=0.186      P=0.128    |  P=0.174      P=0.089      P=0.108      P=0.283    |
|COCHRAN-ARMITAGE       |  P=0.280                                           |  P=0.006 **                                        |
|FISHER EXACT           |               P=0.571      P=0.444      P=0.500    |               P=0.018 *    P=0.001 **   P=0.012 *  |
|=================================================================================================================================|
 (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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