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TDMS Study 05200-06 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                       NITROMETHANE                                     DATE: 04/04/96       
EXPERIMENT: 05200 TEST: 06                                                                                     TIME: 06:24:52       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-75189                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C61927       
PATHOLOGIST: R. MILLER                       R. RENNE                                                          CAS: 75-52-5         
------------------------------------------------------------------------------------------------------------------------------------
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                       NITROMETHANE                                     DATE: 04/04/96       
EXPERIMENT: 05200 TEST: 06                                                                                     TIME: 06:24:52       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-75189                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C61927       
PATHOLOGIST: R. MILLER                       R. RENNE                                                          CAS: 75-52-5         
                                                    MICE(B6C3F1)
                                              ----------------------------
             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 Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    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: Battelle Northwest                                       NITROMETHANE                                     DATE: 04/04/96       
EXPERIMENT: 05200 TEST: 06                                                                                     TIME: 06:24:52       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-75189                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C61927       
PATHOLOGIST: R. MILLER                       R. RENNE                                                          CAS: 75-52-5         
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                          IN THE ANALYSIS OF THE STUDY OF NITROMETHANE
              ====================================================================================================
                                                           MALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Harderian Gland               Adenoma
                                            Carcinoma
                                            Carcinoma or Adenoma
              Liver                         Hepatocellular Carcinoma
              Lung                          Alveolar/Bronchiolar Carcinoma
                                            Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
              All Organs                    Benign Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
                                                           FEMALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Harderian Gland               Adenoma
                                            Carcinoma or Adenoma
              Liver                         Hepatocellular Adenoma
                                            Hepatocellular Carcinoma or Hepatocellular Adenoma
                                            Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
              Lung                          Alveolar/Bronchiolar Adenoma
                                            Alveolar/Bronchiolar Carcinoma
                                            Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
              Pituitary Gland: Pars Distalis or Unspecified Site
                                            Adenoma
              Uterus                        Hemangioma
              All Organs                    Hemangioma
                                            Hemangiosarcoma
                                            Hemangiosarcoma or Hemangioma
                                            Benign Tumors
                                            Malignant Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   1
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/49 (10%)   1/50 (2%)    2/49 (4%)    5/48 (10%) |  1/50 (2%)    0/48 (0%)    1/49 (2%)    1/50 (2%)  |
|ADJUSTED (b)           |  16.1%         2.8%         6.7%        16.4%      |   4.0%         0.0%         3.8%         2.8%      |
|TERMINAL (d)           |  5/31 (16%)   1/36 (3%)    2/30 (7%)    4/28 (14%) |  1/25 (4%)    0/28 (0%)    1/26 (4%)    1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   734 (T)      734 (T)      734 (T)      649       |   734 (T)      ---          734 (T)      734 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.324      P=0.071N     P=0.226N     P=0.576    |  P=0.626      P=0.477N     P=0.754N     P=0.678N   |
|INCIDENTAL TUMOR       |  P=0.341      P=0.071N     P=0.226N     P=0.599    |  P=0.626      P=0.477N     P=0.754N     P=0.678N   |
|LOGISTIC REGRESSION    |  P=0.356      P=0.071N     P=0.226N     P=0.620    |  P=0.626      P=0.477N     P=0.754N     P=0.678N   |
|COCHRAN-ARMITAGE       |  P=0.389                                           |  P=0.542                                           |
|FISHER EXACT           |               P=0.098N     P=0.218N     P=0.617    |               P=0.510N     P=0.747      P=0.753N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/49 (0%)    0/50 (0%)    0/49 (0%)    1/47 (2%)  |  0/50 (0%)    0/48 (0%)    2/49 (4%)    0/49 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         3.6%      |   0.0%         0.0%         7.7%         0.0%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    0/30 (0%)    1/28 (4%)  |  0/25 (0%)    0/28 (0%)    2/26 (8%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          734 (T)   |   ---          ---          734 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.176        (e)          (e)        P=0.480    |  P=0.655        (e)        P=0.246        (e)      |
|INCIDENTAL TUMOR       |  P=0.176        (e)          (e)        P=0.480    |  P=0.655        (e)        P=0.246        (e)      |
|LOGISTIC REGRESSION    |  P=0.176        (e)          (e)        P=0.480    |  P=0.655        (e)        P=0.246        (e)      |
|COCHRAN-ARMITAGE       |  P=0.191                                           |  P=0.593                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.490    |                 (e)        P=0.242        (e)      |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   2
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/49 (0%)    0/50 (0%)    1/49 (2%)    1/47 (2%)  |  0/50 (0%)    0/48 (0%)    2/49 (4%)    0/49 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.2%         3.6%      |   0.0%         0.0%         7.7%         0.0%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    0/30 (0%)    1/28 (4%)  |  0/25 (0%)    0/28 (0%)    2/26 (8%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          534          734 (T)   |   ---          ---          734 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.225        (e)        P=0.500      P=0.480    |  P=0.655        (e)        P=0.246        (e)      |
|INCIDENTAL TUMOR       |  P=0.120        (e)        P=0.500      P=0.480    |  P=0.655        (e)        P=0.246        (e)      |
|LOGISTIC REGRESSION    |  P=0.211        (e)        P=0.581      P=0.480    |  P=0.655        (e)        P=0.246        (e)      |
|COCHRAN-ARMITAGE       |  P=0.226                                           |  P=0.593                                           |
|FISHER EXACT           |                 (e)        P=0.500      P=0.490    |                 (e)        P=0.242        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  0/50 (0%)    1/50 (2%)    2/50 (4%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         3.6%         5.2%         0.0%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    0/30 (0%)    0/29 (0%)  |  0/25 (0%)    1/28 (4%)    0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          734 (T)      568          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.553N     P=0.523      P=0.248        (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.656      P=0.523      P=0.263        (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.622N     P=0.523      P=0.234        (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.616N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.500      P=0.247        (e)      |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   3
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/49 (2%)    2/50 (4%)    0/50 (0%)    0/50 (0%)  |  1/50 (2%)    0/48 (0%)    2/49 (4%)    0/50 (0%)  |
|ADJUSTED (b)           |   3.2%         5.6%         0.0%         0.0%      |   4.0%         0.0%         5.2%         0.0%      |
|TERMINAL (d)           |  1/31 (3%)    2/36 (6%)    0/30 (0%)    0/29 (0%)  |  1/25 (4%)    0/28 (0%)    0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   734 (T)      734 (T)      ---          ---       |   734 (T)      ---          568          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.205N     P=0.552      P=0.507N     P=0.513N   |  P=0.402N     P=0.477N     P=0.513      P=0.427N   |
|INCIDENTAL TUMOR       |  P=0.205N     P=0.552      P=0.507N     P=0.513N   |  P=0.502N     P=0.477N     P=0.515      P=0.427N   |
|LOGISTIC REGRESSION    |  P=0.205N     P=0.552      P=0.507N     P=0.513N   |  P=0.463N     P=0.477N     P=0.492      P=0.427N   |
|COCHRAN-ARMITAGE       |  P=0.185N                                          |  P=0.458N                                          |
|FISHER EXACT           |               P=0.508      P=0.495N     P=0.495N   |               P=0.510N     P=0.492      P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  9/50 (18%)  10/50 (20%)  19/50 (38%)  32/50 (64%) |  5/50 (10%)   7/50 (14%)  16/50 (32%)  19/50 (38%) |
|ADJUSTED (b)           |  26.6%        22.8%        51.9%        75.5%      |  16.0%        21.4%        43.1%        45.9%      |
|TERMINAL (d)           |  7/31 (23%)   4/36 (11%)  13/30 (43%)  19/29 (66%) |  2/25 (8%)    4/28 (14%)   7/26 (27%)  14/36 (39%) |
|FIRST INCIDENCE (DAYS) |   545          448          520          497       |   609          639          498          503       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.555N     P=0.023 *    P<0.001 ** |  P=0.008 **   P=0.413      P=0.016 *    P=0.020 *  |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.471      P=0.018 *    P<0.001 ** |  P<0.001 **   P=0.345      P=0.007 **   P=0.002 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.505      P=0.019 *    P<0.001 ** |  P<0.001 **   P=0.380      P=0.008 **   P=0.003 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.500      P=0.022 *    P<0.001 ** |               P=0.380      P=0.006 **   P<0.001 ** |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   4
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    1/50 (2%)    6/50 (12%)   5/50 (10%) |  1/50 (2%)    2/50 (4%)    4/50 (8%)    3/50 (6%)  |
|ADJUSTED (b)           |   2.6%         2.8%        16.5%        14.7%      |   2.9%         6.7%        14.1%         8.3%      |
|TERMINAL (d)           |  0/31 (0%)    1/36 (3%)    3/30 (10%)   3/29 (10%) |  0/25 (0%)    1/28 (4%)    3/26 (12%)   3/36 (8%)  |
|FIRST INCIDENCE (DAYS) |   653          734 (T)      436          595       |   663          693          679          734 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.031 *    P=0.730N     P=0.060      P=0.108    |  P=0.364      P=0.506      P=0.195      P=0.425    |
|INCIDENTAL TUMOR       |  P=0.052      P=0.730N     P=0.061      P=0.147    |  P=0.284      P=0.439      P=0.198      P=0.363    |
|LOGISTIC REGRESSION    |  P=0.036 *    P=0.762N     P=0.062      P=0.104    |  P=0.305      P=0.501      P=0.194      P=0.365    |
|COCHRAN-ARMITAGE       |  P=0.036 *                                         |  P=0.221                                           |
|FISHER EXACT           |               P=0.753N     P=0.056      P=0.102    |               P=0.500      P=0.181      P=0.309    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/50 (20%)  11/50 (22%)  25/50 (50%)  37/50 (74%) |  6/50 (12%)   9/50 (18%)  20/50 (40%)  21/50 (42%) |
|ADJUSTED (b)           |  28.4%        25.3%        63.2%        83.7%      |  18.4%        27.1%        53.5%        50.8%      |
|TERMINAL (d)           |  7/31 (23%)   5/36 (14%)  16/30 (53%)  22/29 (76%) |  2/25 (8%)    5/28 (18%)  10/26 (38%)  16/36 (44%) |
|FIRST INCIDENCE (DAYS) |   545          448          436          497       |   609          639          498          503       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.540N     P=0.003 **   P<0.001 ** |  P=0.010 *    P=0.324      P=0.005 **   P=0.019 *  |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.485      P=0.001 **   P<0.001 ** |  P<0.001 **   P=0.233      P=0.002 **   P=0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.506      P=0.001 **   P<0.001 ** |  P<0.001 **   P=0.175      P=0.002 **   P=0.002 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.500      P=0.002 **   P<0.001 ** |               P=0.288      P=0.001 **   P<0.001 ** |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   5
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/49 (2%)    3/50 (6%)    0/49 (0%)    1/49 (2%)  |  0/50 (0%)    0/48 (0%)    0/47 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |   2.2%         7.8%         0.0%         2.4%      |   0.0%         0.0%         0.0%         2.2%      |
|TERMINAL (d)           |  0/31 (0%)    2/36 (6%)    0/30 (0%)    0/29 (0%)  |  0/25 (0%)    0/28 (0%)    0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   534          679          ---          632       |   ---          ---          ---          632       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.421N     P=0.356      P=0.500N     P=0.747N   |  P=0.223        (e)          (e)        P=0.534    |
|INCIDENTAL TUMOR       |  P=0.400N     P=0.283      P=0.536N     P=0.704    |  P=0.126        (e)          (e)        P=0.362    |
|LOGISTIC REGRESSION    |  P=0.416N     P=0.300      P=0.425N     P=0.734    |  P=0.193        (e)          (e)        P=0.486    |
|COCHRAN-ARMITAGE       |  P=0.412N                                          |  P=0.202                                           |
|FISHER EXACT           |               P=0.316      P=0.500N     P=0.753N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    2/50 (4%)    2/50 (4%)    0/50 (0%)  |  2/50 (4%)    0/49 (0%)    2/49 (4%)    0/50 (0%)  |
|ADJUSTED (b)           |   3.2%         5.2%         6.7%         0.0%      |   7.4%         0.0%         6.9%         0.0%      |
|TERMINAL (d)           |  1/31 (3%)    1/36 (3%)    2/30 (7%)    0/29 (0%)  |  1/25 (4%)    0/28 (0%)    1/26 (4%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   734 (T)      721          734 (T)      ---       |   707          ---          693          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.330N     P=0.560      P=0.488      P=0.513N   |  P=0.184N     P=0.224N     P=0.676N     P=0.167N   |
|INCIDENTAL TUMOR       |  P=0.300N     P=0.548      P=0.488      P=0.513N   |  P=0.239N     P=0.261N     P=0.672N     P=0.245N   |
|LOGISTIC REGRESSION    |  P=0.319N     P=0.559      P=0.488      P=0.513N   |  P=0.203N     P=0.234N     P=0.676N     P=0.190N   |
|COCHRAN-ARMITAGE       |  P=0.296N                                          |  P=0.247N                                          |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.500N   |               P=0.253N     P=0.684      P=0.247N   |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   6
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 17/50 (34%)  14/50 (28%)  13/50 (26%)  17/50 (34%) | 14/50 (28%)  25/49 (51%)  17/49 (35%)  35/50 (70%) |
|ADJUSTED (b)           |  44.2%        38.9%        36.2%        52.5%      |  45.5%        68.6%        49.0%        83.1%      |
|TERMINAL (d)           | 11/31 (35%)  14/36 (39%)   8/30 (27%)  14/29 (48%) |  9/25 (36%)  17/28 (61%)  10/26 (38%)  29/36 (81%) |
|FIRST INCIDENCE (DAYS) |   449          734 (T)      436          679       |   597          534          498          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.352      P=0.196N     P=0.300N     P=0.522    |  P=0.022 *    P=0.048 *    P=0.395      P=0.009 ** |
|INCIDENTAL TUMOR       |  P=0.381      P=0.297N     P=0.300N     P=0.462    |  P<0.001 **   P=0.014 *    P=0.332      P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.484      P=0.292N     P=0.261N     P=0.562N   |  P<0.001 **   P=0.013 *    P=0.364      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.490                                           |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.333N     P=0.257N     P=0.583N   |               P=0.016 *    P=0.308      P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/50 (32%)  14/50 (28%)  10/50 (20%)   9/50 (18%) | 10/50 (20%)  14/49 (29%)   8/49 (16%)  12/50 (24%) |
|ADJUSTED (b)           |  35.6%        33.3%        21.9%        20.7%      |  29.7%        35.7%        26.6%        25.6%      |
|TERMINAL (d)           |  5/31 (16%)   9/36 (25%)   1/30 (3%)    2/29 (7%)  |  3/25 (12%)   6/28 (21%)   6/26 (23%)   2/36 (6%)  |
|FIRST INCIDENCE (DAYS) |   441          448          377          406       |   576          534          548          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.085N     P=0.297N     P=0.177N     P=0.104N   |  P=0.322N     P=0.296      P=0.362N     P=0.495N   |
|INCIDENTAL TUMOR       |  P=0.022N*    P=0.505      P=0.090N     P=0.065N   |  P=0.302      P=0.160      P=0.359N     P=0.091    |
|LOGISTIC REGRESSION    |  P=0.032N*    P=0.440      P=0.120N     P=0.099N   |  P=0.329      P=0.195      P=0.383N     P=0.200    |
|COCHRAN-ARMITAGE       |  P=0.051N                                          |  P=0.505                                           |
|FISHER EXACT           |               P=0.414N     P=0.127N     P=0.083N   |               P=0.224      P=0.416N     P=0.405    |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   7
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 29/50 (58%)  24/50 (48%)  22/50 (44%)  26/50 (52%) | 19/50 (38%)  34/49 (69%)  22/49 (45%)  40/50 (80%) |
|ADJUSTED (b)           |  60.6%        58.0%        48.4%        64.9%      |  54.6%        82.4%        62.6%        86.9%      |
|TERMINAL (d)           | 13/31 (42%)  19/36 (53%)   8/30 (27%)  16/29 (55%) | 10/25 (40%)  21/28 (75%)  14/26 (54%)  30/36 (83%) |
|FIRST INCIDENCE (DAYS) |   441          448          377          406       |   576          534          498          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.502N     P=0.119N     P=0.210N     P=0.405N   |  P=0.095      P=0.018 *    P=0.420      P=0.032 *  |
|INCIDENTAL TUMOR       |  P=0.344N     P=0.393N     P=0.104N     P=0.432N   |  P<0.001 **   P<0.001 **   P=0.355      P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.319N     P=0.268N     P=0.111N     P=0.383N   |  P=0.001 **   P<0.001 **   P=0.368      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.360N                                          |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.212N     P=0.115N     P=0.344N   |               P=0.002 **   P=0.311      P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 29/50 (58%)  24/50 (48%)  22/50 (44%)  26/50 (52%) | 19/50 (38%)  34/49 (69%)  22/49 (45%)  40/50 (80%) |
|ADJUSTED (b)           |  60.6%        58.0%        48.4%        64.9%      |  54.6%        82.4%        62.6%        86.9%      |
|TERMINAL (d)           | 13/31 (42%)  19/36 (53%)   8/30 (27%)  16/29 (55%) | 10/25 (40%)  21/28 (75%)  14/26 (54%)  30/36 (83%) |
|FIRST INCIDENCE (DAYS) |   441          448          377          406       |   576          534          498          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.502N     P=0.119N     P=0.210N     P=0.405N   |  P=0.095      P=0.018 *    P=0.420      P=0.032 *  |
|INCIDENTAL TUMOR       |  P=0.344N     P=0.393N     P=0.104N     P=0.432N   |  P<0.001 **   P<0.001 **   P=0.355      P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.319N     P=0.268N     P=0.111N     P=0.383N   |  P=0.001 **   P<0.001 **   P=0.368      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.360N                                          |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.212N     P=0.115N     P=0.344N   |               P=0.002 **   P=0.311      P<0.001 ** |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   8
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/50 (22%)  10/50 (20%)   9/50 (18%)  12/50 (24%) |  3/50 (6%)    3/50 (6%)    2/49 (4%)    9/50 (18%) |
|ADJUSTED (b)           |  30.8%        26.0%        30.0%        35.1%      |  11.5%        10.7%         4.3%        22.7%      |
|TERMINAL (d)           |  8/31 (26%)   8/36 (22%)   9/30 (30%)   8/29 (28%) |  2/25 (8%)    3/28 (11%)   0/26 (0%)    6/36 (17%) |
|FIRST INCIDENCE (DAYS) |   449          646          734 (T)      497       |   716          734 (T)      498          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.322      P=0.365N     P=0.433N     P=0.456    |  P=0.065      P=0.610N     P=0.466N     P=0.186    |
|INCIDENTAL TUMOR       |  P=0.388      P=0.464N     P=0.424N     P=0.468    |  P=0.020 *    P=0.644N     P=0.608N     P=0.072    |
|LOGISTIC REGRESSION    |  P=0.422      P=0.456N     P=0.412N     P=0.511    |  P=0.022 *    P=0.632N     P=0.514N     P=0.083    |
|COCHRAN-ARMITAGE       |  P=0.430                                           |  P=0.018 *                                         |
|FISHER EXACT           |               P=0.500N     P=0.402N     P=0.500    |               P=0.661N     P=0.510N     P=0.061    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    3/50 (6%)    3/50 (6%)   11/50 (22%) |  0/50 (0%)    3/50 (6%)    5/49 (10%)   3/50 (6%)  |
|ADJUSTED (b)           |   6.5%         8.3%        10.0%        30.4%      |   0.0%         8.3%        15.0%         7.2%      |
|TERMINAL (d)           |  2/31 (6%)    3/36 (8%)    3/30 (10%)   6/29 (21%) |  0/25 (0%)    1/28 (4%)    2/26 (8%)    1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   734 (T)      734 (T)      734 (T)      586       |   ---          534          602          503       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.569      P=0.485      P=0.009 ** |  P=0.264      P=0.134      P=0.041 *    P=0.178    |
|INCIDENTAL TUMOR       |  P=0.002 **   P=0.569      P=0.485      P=0.015 *  |  P=0.088      P=0.117      P=0.040 *    P=0.068    |
|LOGISTIC REGRESSION    |  P=0.001 **   P=0.569      P=0.485      P=0.009 ** |  P=0.149      P=0.119      P=0.033 *    P=0.110    |
|COCHRAN-ARMITAGE       |  P=0.001 **                                        |  P=0.159                                           |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.007 ** |               P=0.121      P=0.027 *    P=0.121    |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE   9
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/50 (26%)  13/50 (26%)  12/50 (24%)  20/50 (40%) |  3/50 (6%)    6/50 (12%)   6/49 (12%)  12/50 (24%) |
|ADJUSTED (b)           |  36.8%        33.9%        40.0%        51.2%      |  11.5%        18.5%        16.8%        28.7%      |
|TERMINAL (d)           | 10/31 (32%)  11/36 (31%)  12/30 (40%)  11/29 (38%) |  2/25 (8%)    4/28 (14%)   2/26 (8%)    7/36 (19%) |
|FIRST INCIDENCE (DAYS) |   449          646          734 (T)      497       |   716          534          498          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.032 *    P=0.427N     P=0.540N     P=0.099    |  P=0.042 *    P=0.293      P=0.280      P=0.066    |
|INCIDENTAL TUMOR       |  P=0.062      P=0.524N     P=0.531N     P=0.119    |  P=0.004 **   P=0.252      P=0.193      P=0.010 ** |
|LOGISTIC REGRESSION    |  P=0.059      P=0.517N     P=0.515N     P=0.105    |  P=0.007 **   P=0.243      P=0.238      P=0.015 *  |
|COCHRAN-ARMITAGE       |  P=0.063                                           |  P=0.007 **                                        |
|FISHER EXACT           |               P=0.590N     P=0.500N     P=0.101    |               P=0.243      P=0.233      P=0.011 *  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  2/50 (4%)    2/50 (4%)    2/50 (4%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   6.8%         5.9%         5.0%         0.0%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    0/30 (0%)    0/29 (0%)  |  1/25 (4%)    1/28 (4%)    0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   667          569          548          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.124N     P=0.685N     P=0.677N     P=0.179N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.193N     P=0.685      P=0.664N     P=0.245N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.170N     P=0.695N     P=0.693      P=0.217N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.163N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.691N     P=0.691N     P=0.247N   |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  10
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  2/50 (4%)    2/50 (4%)    3/50 (6%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   6.8%         5.9%         7.6%         0.0%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    0/30 (0%)    0/29 (0%)  |  1/25 (4%)    1/28 (4%)    0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   667          569          548          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.151N     P=0.685N     P=0.517      P=0.179N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.244N     P=0.685      P=0.538      P=0.245N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.208N     P=0.695N     P=0.497      P=0.217N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.199N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.691N     P=0.500      P=0.247N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  2/50 (4%)    2/50 (4%)    3/50 (6%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   6.8%         5.9%         7.6%         0.0%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    0/30 (0%)    0/29 (0%)  |  1/25 (4%)    1/28 (4%)    0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   667          569          548          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.151N     P=0.685N     P=0.517      P=0.179N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.244N     P=0.685      P=0.538      P=0.245N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.208N     P=0.695N     P=0.497      P=0.217N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.199N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.691N     P=0.500      P=0.247N   |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  11
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/47 (4%)    1/47 (2%)    0/48 (0%)    3/48 (6%)  |
|ADJUSTED (b)           |                                                    |   4.9%         3.6%         0.0%         8.1%      |
|TERMINAL (d)           |                                                    |  0/24 (0%)    1/28 (4%)    0/26 (0%)    2/34 (6%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   576          734 (T)      ---          687       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.433      P=0.491N     P=0.232N     P=0.609    |
|INCIDENTAL TUMOR       |                                                    |  P=0.322      P=0.550N     P=0.232N     P=0.417    |
|LOGISTIC REGRESSION    |                                                    |  P=0.354      P=0.502N     P=0.236N     P=0.505    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.345                                           |
|FISHER EXACT           |                                                    |               P=0.500N     P=0.242N     P=0.510    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Granulosa Cell Tumor Benign                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/47 (0%)    2/47 (4%)    0/48 (0%)    0/48 (0%)  |
|ADJUSTED (b)           |                                                    |   0.0%         6.7%         0.0%         0.0%      |
|TERMINAL (d)           |                                                    |  0/24 (0%)    1/28 (4%)    0/26 (0%)    0/34 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          693          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.348N     P=0.257        (e)          (e)      |
|INCIDENTAL TUMOR       |                                                    |  P=0.386N     P=0.228        (e)          (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.369N     P=0.244        (e)          (e)      |
|COCHRAN-ARMITAGE       |                                                    |  P=0.401N                                          |
|FISHER EXACT           |                                                    |               P=0.247        (e)          (e)      |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  12
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/47 (2%)    0/50 (0%)    0/46 (0%)    0/47 (0%)  |  9/50 (18%)  10/46 (22%)   8/48 (17%)   4/50 (8%)  |
|ADJUSTED (b)           |   2.4%         0.0%         0.0%         0.0%      |  30.3%        33.9%        32.0%        10.8%      |
|TERMINAL (d)           |  0/29 (0%)    0/36 (0%)    0/29 (0%)    0/29 (0%)  |  6/25 (24%)   8/27 (30%)   8/25 (32%)   3/36 (8%)  |
|FIRST INCIDENCE (DAYS) |   609          ---          ---          ---       |   597          656          734 (T)      729       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.306N     P=0.481N     P=0.515N     P=0.491N   |  P=0.014N*    P=0.544      P=0.494N     P=0.036N*  |
|INCIDENTAL TUMOR       |  P=0.227N     P=0.773N     P=0.455N     P=0.419N   |  P=0.022N*    P=0.475      P=0.490N     P=0.081N   |
|LOGISTIC REGRESSION    |  P=0.315N     P=0.506N     P=0.490N     P=0.536N   |  P=0.019N*    P=0.456      P=0.470N     P=0.063N   |
|COCHRAN-ARMITAGE       |  P=0.308N                                          |  P=0.064N                                          |
|FISHER EXACT           |               P=0.485N     P=0.505N     P=0.500N   |               P=0.419      P=0.537N     P=0.117N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |  0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         3.3%         0.0%      |   0.0%         0.0%         6.9%         0.0%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    1/30 (3%)    0/29 (0%)  |  0/25 (0%)    0/28 (0%)    1/26 (4%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          734 (T)      ---       |   ---          ---          693          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.682        (e)        P=0.493        (e)      |  P=0.655        (e)        P=0.248        (e)      |
|INCIDENTAL TUMOR       |  P=0.682        (e)        P=0.493        (e)      |  P=0.601        (e)        P=0.254        (e)      |
|LOGISTIC REGRESSION    |  P=0.682        (e)        P=0.493        (e)      |  P=0.631        (e)        P=0.250        (e)      |
|COCHRAN-ARMITAGE       |  P=0.695                                           |  P=0.595                                           |
|FISHER EXACT           |                 (e)        P=0.500        (e)      |                 (e)        P=0.247        (e)      |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  13
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  1/50 (2%)    1/50 (2%)    1/50 (2%)    2/50 (4%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   3.2%         2.6%         3.3%         4.4%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    0/30 (0%)    0/29 (0%)  |  0/25 (0%)    0/28 (0%)    0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   693          637          716          553       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.431      P=0.754N     P=0.741N     P=0.563    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.193      P=0.725      P=0.746N     P=0.290    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.334      P=0.762N     P=0.753N     P=0.474    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.351                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.753N     P=0.753N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    0/50 (0%)    1/50 (2%)  |  1/50 (2%)    1/50 (2%)    0/50 (0%)    2/50 (4%)  |
|ADJUSTED (b)           |   0.0%         5.3%         0.0%         3.4%      |   4.0%         3.6%         0.0%         5.6%      |
|TERMINAL (d)           |  0/31 (0%)    1/36 (3%)    0/30 (0%)    1/29 (3%)  |  1/25 (4%)    1/28 (4%)    0/26 (0%)    2/36 (6%)  |
|FIRST INCIDENCE (DAYS) |   ---          728          ---          734 (T)   |   734 (T)      734 (T)      ---          734 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.504      P=0.276        (e)        P=0.487    |  P=0.473      P=0.737N     P=0.492N     P=0.627    |
|INCIDENTAL TUMOR       |  P=0.552      P=0.270        (e)        P=0.487    |  P=0.473      P=0.737N     P=0.492N     P=0.627    |
|LOGISTIC REGRESSION    |  P=0.513      P=0.277        (e)        P=0.487    |  P=0.473      P=0.737N     P=0.492N     P=0.627    |
|COCHRAN-ARMITAGE       |  P=0.539                                           |  P=0.366                                           |
|FISHER EXACT           |               P=0.247        (e)        P=0.500    |               P=0.753N     P=0.500N     P=0.500    |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  14
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)  |  1/50 (2%)    1/50 (2%)    0/50 (0%)    2/50 (4%)  |
|ADJUSTED (b)           |   0.0%         2.8%         0.0%         3.4%      |   4.0%         3.6%         0.0%         5.6%      |
|TERMINAL (d)           |  0/31 (0%)    1/36 (3%)    0/30 (0%)    1/29 (3%)  |  1/25 (4%)    1/28 (4%)    0/26 (0%)    2/36 (6%)  |
|FIRST INCIDENCE (DAYS) |   ---          734 (T)      ---          734 (T)   |   734 (T)      734 (T)      ---          734 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.377      P=0.530        (e)        P=0.487    |  P=0.473      P=0.737N     P=0.492N     P=0.627    |
|INCIDENTAL TUMOR       |  P=0.377      P=0.530        (e)        P=0.487    |  P=0.473      P=0.737N     P=0.492N     P=0.627    |
|LOGISTIC REGRESSION    |  P=0.377      P=0.530        (e)        P=0.487    |  P=0.473      P=0.737N     P=0.492N     P=0.627    |
|COCHRAN-ARMITAGE       |  P=0.405                                           |  P=0.366                                           |
|FISHER EXACT           |               P=0.500        (e)        P=0.500    |               P=0.753N     P=0.500N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    1/50 (2%)    1/50 (2%)    1/50 (2%)  |                                                    |
|ADJUSTED (b)           |   6.5%         2.7%         3.3%         3.4%      |                                                    |
|TERMINAL (d)           |  2/31 (6%)    0/36 (0%)    1/30 (3%)    1/29 (3%)  |                                                    |
|FIRST INCIDENCE (DAYS) |   734 (T)      731          734 (T)      734 (T)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.450N     P=0.449N     P=0.512N     P=0.523N   |                                                    |
|INCIDENTAL TUMOR       |  P=0.414N     P=0.452N     P=0.512N     P=0.523N   |                                                    |
|LOGISTIC REGRESSION    |  P=0.451N     P=0.436N     P=0.512N     P=0.523N   |                                                    |
|COCHRAN-ARMITAGE       |  P=0.409N                                          |                                                    |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.500N   |                                                    |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  15
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    0/50 (0%)    0/49 (0%)    1/48 (2%)  |  4/50 (8%)    1/48 (2%)    1/48 (2%)    1/50 (2%)  |
|ADJUSTED (b)           |   3.2%         0.0%         0.0%         3.4%      |  12.2%         2.6%         4.0%         2.8%      |
|TERMINAL (d)           |  1/31 (3%)    0/36 (0%)    0/30 (0%)    1/29 (3%)  |  2/25 (8%)    0/28 (0%)    1/25 (4%)    1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   734 (T)      ---          ---          734 (T)   |   385          581          734 (T)      734 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.571      P=0.470N     P=0.507N     P=0.747    |  P=0.096N     P=0.177N     P=0.180N     P=0.116N   |
|INCIDENTAL TUMOR       |  P=0.571      P=0.470N     P=0.507N     P=0.747    |  P=0.156N     P=0.216N     P=0.263N     P=0.201N   |
|LOGISTIC REGRESSION    |  P=0.571      P=0.470N     P=0.507N     P=0.747    |  P=0.144N     P=0.196N     P=0.196N     P=0.198N   |
|COCHRAN-ARMITAGE       |  P=0.587                                           |  P=0.134N                                          |
|FISHER EXACT           |               P=0.500N     P=0.505N     P=0.742    |               P=0.194N     P=0.194N     P=0.181N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    1/50 (2%)    0/49 (0%)    1/48 (2%)  |  4/50 (8%)    1/48 (2%)    1/48 (2%)    1/50 (2%)  |
|ADJUSTED (b)           |   3.2%         2.8%         0.0%         3.4%      |  12.2%         2.6%         4.0%         2.8%      |
|TERMINAL (d)           |  1/31 (3%)    1/36 (3%)    0/30 (0%)    1/29 (3%)  |  2/25 (8%)    0/28 (0%)    1/25 (4%)    1/36 (3%)  |
|FIRST INCIDENCE (DAYS) |   734 (T)      734 (T)      ---          734 (T)   |   385          581          734 (T)      734 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.649N     P=0.728N     P=0.507N     P=0.747    |  P=0.096N     P=0.177N     P=0.180N     P=0.116N   |
|INCIDENTAL TUMOR       |  P=0.649N     P=0.728N     P=0.507N     P=0.747    |  P=0.156N     P=0.216N     P=0.263N     P=0.201N   |
|LOGISTIC REGRESSION    |  P=0.649N     P=0.728N     P=0.507N     P=0.747    |  P=0.144N     P=0.196N     P=0.196N     P=0.198N   |
|COCHRAN-ARMITAGE       |  P=0.627N                                          |  P=0.134N                                          |
|FISHER EXACT           |               P=0.753N     P=0.505N     P=0.742    |               P=0.194N     P=0.194N     P=0.181N   |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  16
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/50 (4%)    5/50 (10%)   0/50 (0%)    0/50 (0%)  |
|ADJUSTED (b)           |                                                    |   6.3%        15.7%         0.0%         0.0%      |
|TERMINAL (d)           |                                                    |  1/25 (4%)    3/28 (11%)   0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   597          569          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.034N*    P=0.239      P=0.230N     P=0.191N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.049N*    P=0.226      P=0.223N     P=0.267N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.048N*    P=0.217      P=0.238N     P=0.242N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.052N                                          |
|FISHER EXACT           |                                                    |               P=0.218      P=0.247N     P=0.247N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  4/50 (8%)    2/50 (4%)    1/50 (2%)    3/50 (6%)  |
|ADJUSTED (b)           |                                                    |  14.0%         7.1%         3.8%         8.0%      |
|TERMINAL (d)           |                                                    |  3/25 (12%)   2/28 (7%)    1/26 (4%)    2/36 (6%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   576          734 (T)      734 (T)      721       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.308N     P=0.299N     P=0.169N     P=0.327N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.363N     P=0.294N     P=0.164N     P=0.445N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.361N     P=0.333N     P=0.166N     P=0.431N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.456N                                          |
|FISHER EXACT           |                                                    |               P=0.339N     P=0.181N     P=0.500N   |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  17
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  3/50 (6%)    6/50 (12%)   0/50 (0%)    1/50 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  10.2%        19.0%         0.0%         2.4%      |
|TERMINAL (d)           |  0/31 (0%)    0/36 (0%)    0/30 (0%)    0/29 (0%)  |  2/25 (8%)    4/28 (14%)   0/26 (0%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   597          569          ---          687       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.044N*    P=0.275      P=0.115N     P=0.215N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.068N     P=0.263      P=0.111N     P=0.339N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.064N     P=0.243      P=0.116N     P=0.292N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.077N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.243      P=0.121N     P=0.309N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    4/50 (8%)    2/50 (4%)    0/50 (0%)  |  4/50 (8%)    1/50 (2%)    5/50 (10%)   0/50 (0%)  |
|ADJUSTED (b)           |   3.2%        10.6%         6.7%         0.0%      |  15.1%         3.6%        16.2%         0.0%      |
|TERMINAL (d)           |  1/31 (3%)    3/36 (8%)    2/30 (7%)    0/29 (0%)  |  3/25 (12%)   1/28 (4%)    3/26 (12%)   0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   734 (T)      721          734 (T)      ---       |   707          734 (T)      568          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.231N     P=0.234      P=0.488      P=0.513N   |  P=0.063N     P=0.152N     P=0.526      P=0.028N*  |
|INCIDENTAL TUMOR       |  P=0.210N     P=0.227      P=0.488      P=0.513N   |  P=0.087N     P=0.171N     P=0.536      P=0.043N*  |
|LOGISTIC REGRESSION    |  P=0.222N     P=0.235      P=0.488      P=0.513N   |  P=0.081N     P=0.160N     P=0.533      P=0.031N*  |
|COCHRAN-ARMITAGE       |  P=0.199N                                          |  P=0.114N                                          |
|FISHER EXACT           |               P=0.181      P=0.500      P=0.500N   |               P=0.181N     P=0.500      P=0.059N   |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  18
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    4/50 (8%)    2/50 (4%)    0/50 (0%)  |  7/50 (14%)   7/50 (14%)   5/50 (10%)   1/50 (2%)  |
|ADJUSTED (b)           |   3.2%        10.6%         6.7%         0.0%      |  24.7%        22.4%        16.2%         2.4%      |
|TERMINAL (d)           |  1/31 (3%)    3/36 (8%)    2/30 (7%)    0/29 (0%)  |  5/25 (20%)   5/28 (18%)   3/26 (12%)   0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   734 (T)      721          734 (T)      ---       |   597          569          568          687       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.231N     P=0.234      P=0.488      P=0.513N   |  P=0.006N**   P=0.556N     P=0.352N     P=0.011N*  |
|INCIDENTAL TUMOR       |  P=0.210N     P=0.227      P=0.488      P=0.513N   |  P=0.013N*    P=0.586N     P=0.338N     P=0.028N*  |
|LOGISTIC REGRESSION    |  P=0.222N     P=0.235      P=0.488      P=0.513N   |  P=0.011N*    P=0.612N     P=0.347N     P=0.020N*  |
|COCHRAN-ARMITAGE       |  P=0.199N                                          |  P=0.019N*                                         |
|FISHER EXACT           |               P=0.181      P=0.500      P=0.500N   |               P=0.613N     P=0.380N     P=0.030N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    0/50 (0%)    3/50 (6%)    1/50 (2%)  |  2/50 (4%)    0/50 (0%)    3/50 (6%)    0/50 (0%)  |
|ADJUSTED (b)           |   8.7%         0.0%         8.6%         3.4%      |   7.1%         0.0%         9.7%         0.0%      |
|TERMINAL (d)           |  1/31 (3%)    0/36 (0%)    1/30 (3%)    1/29 (3%)  |  1/25 (4%)    0/28 (0%)    1/26 (4%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   653          ---          563          734 (T)   |   693          ---          631          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.405N     P=0.101N     P=0.648      P=0.326N   |  P=0.221N     P=0.227N     P=0.524      P=0.172N   |
|INCIDENTAL TUMOR       |  P=0.292N     P=0.098N     P=0.652N     P=0.247N   |  P=0.318N     P=0.261N     P=0.533      P=0.245N   |
|LOGISTIC REGRESSION    |  P=0.373N     P=0.110N     P=0.659      P=0.297N   |  P=0.260N     P=0.235N     P=0.522      P=0.201N   |
|COCHRAN-ARMITAGE       |  P=0.372N                                          |  P=0.296N                                          |
|FISHER EXACT           |               P=0.121N     P=0.661N     P=0.309N   |               P=0.247N     P=0.500      P=0.247N   |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  19
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated                                               |
|     Cell Type                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    4/50 (8%)    2/50 (4%)    1/50 (2%)  |  9/50 (18%)   7/50 (14%)   7/50 (14%)   7/50 (14%) |
|ADJUSTED (b)           |   8.4%         9.6%         6.3%         2.4%      |  23.4%        20.7%        21.3%        17.5%      |
|TERMINAL (d)           |  2/31 (6%)    1/36 (3%)    1/30 (3%)    0/29 (0%)  |  2/25 (8%)    4/28 (14%)   3/26 (12%)   4/36 (11%) |
|FIRST INCIDENCE (DAYS) |   490          479          707          649       |   385          416          609          603       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.187N     P=0.558      P=0.511N     P=0.315N   |  P=0.196N     P=0.382N     P=0.368N     P=0.223N   |
|INCIDENTAL TUMOR       |  P=0.163N     P=0.427      P=0.523N     P=0.353N   |  P=0.492N     P=0.442N     P=0.476N     P=0.612N   |
|LOGISTIC REGRESSION    |  P=0.162N     P=0.465      P=0.501N     P=0.315N   |  P=0.389N     P=0.397N     P=0.404N     P=0.440N   |
|COCHRAN-ARMITAGE       |  P=0.162N                                          |  P=0.369N                                          |
|FISHER EXACT           |               P=0.500      P=0.500N     P=0.309N   |               P=0.393N     P=0.393N     P=0.393N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 31/50 (62%)  31/50 (62%)  33/50 (66%)  43/50 (86%) | 31/50 (62%)  39/50 (78%)  33/50 (66%)  43/50 (86%) |
|ADJUSTED (b)           |  74.9%        67.3%        84.3%        95.5%      |  78.8%        95.1%        86.2%        91.4%      |
|TERMINAL (d)           | 21/31 (68%)  21/36 (58%)  24/30 (80%)  27/29 (93%) | 17/25 (68%)  26/28 (93%)  21/26 (81%)  32/36 (89%) |
|FIRST INCIDENCE (DAYS) |   449          448          436          497       |   385          534          498           51       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.003 **   P=0.289N     P=0.364      P=0.020 *  |  P=0.422N     P=0.208      P=0.522      P=0.533    |
|INCIDENTAL TUMOR       |  P=0.004 **   P=0.580N     P=0.355      P=0.008 ** |  P=0.047 *    P=0.042 *    P=0.464      P=0.018 *  |
|LOGISTIC REGRESSION    |  P=0.002 **   P=0.521N     P=0.378      P=0.007 ** |  P=0.041 *    P=0.043 *    P=0.512      P=0.011 *  |
|COCHRAN-ARMITAGE       |  P=0.003 **                                        |  P=0.014 *                                         |
|FISHER EXACT           |               P=0.582N     P=0.418      P=0.006 ** |               P=0.063      P=0.418      P=0.006 ** |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  20
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      188 PPM      375 PPM      750 PPM   |   CONTROL      188 PPM      375 PPM      750 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 22/50 (44%)  25/50 (50%)  24/50 (48%)  22/50 (44%) | 26/50 (52%)  24/50 (48%)  28/50 (56%)  21/50 (42%) |
|ADJUSTED (b)           |  48.3%        55.3%        51.9%        50.0%      |  61.1%        56.6%        67.4%        42.9%      |
|TERMINAL (d)           |  9/31 (29%)  16/36 (44%)   9/30 (30%)   9/29 (31%) |  9/25 (36%)  11/28 (39%)  13/26 (50%)   8/36 (22%) |
|FIRST INCIDENCE (DAYS) |   441          448          377          406       |   385          416          548          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.489      P=0.559      P=0.403      P=0.556    |  P=0.048N*    P=0.385N     P=0.515      P=0.055N   |
|INCIDENTAL TUMOR       |  P=0.360N     P=0.162      P=0.389      P=0.552N   |  P=0.465N     P=0.518N     P=0.464      P=0.545    |
|LOGISTIC REGRESSION    |  P=0.407N     P=0.145      P=0.343      P=0.534    |  P=0.404N     P=0.398N     P=0.462      P=0.520N   |
|COCHRAN-ARMITAGE       |  P=0.472N                                          |  P=0.215N                                          |
|FISHER EXACT           |               P=0.344      P=0.421      P=0.580N   |               P=0.421N     P=0.421      P=0.212N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 40/50 (80%)  39/50 (78%)  43/50 (86%)  46/50 (92%) | 38/50 (76%)  45/50 (90%)  43/50 (86%)  46/50 (92%) |
|ADJUSTED (b)           |  83.0%        81.2%        89.5%        95.8%      |  86.2%       100.0%        97.7%        92.0%      |
|TERMINAL (d)           | 23/31 (74%)  27/36 (75%)  25/30 (83%)  27/29 (93%) | 19/25 (76%)  28/28 (100%) 25/26 (96%)  32/36 (89%) |
|FIRST INCIDENCE (DAYS) |   441          448          377          406       |   385          416          498           51       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.057      P=0.209N     P=0.322      P=0.178    |  P=0.157N     P=0.288      P=0.368      P=0.286N   |
|INCIDENTAL TUMOR       |  P=0.049 *    P=0.501      P=0.220      P=0.079    |  P=0.059      P=0.024 *    P=0.165      P=0.025 *  |
|LOGISTIC REGRESSION    |  P=0.032 *    P=0.523N     P=0.211      P=0.070    |  P=0.070      P=0.040 *    P=0.198      P=0.040 *  |
|COCHRAN-ARMITAGE       |  P=0.034 *                                         |  P=0.037 *                                         |
|FISHER EXACT           |               P=0.500N     P=0.298      P=0.074    |               P=0.054      P=0.154      P=0.027 *  |
|=================================================================================================================================|
         DATE: 04/04/96                     EXPERIMENT: 05200 TEST: 06                                                 PAGE  21
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NITROMETHANE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).