NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Midwest Research Inst                                 TETRANITROMETHANE                                   DATE: 09/09/94       
EXPERIMENT: 05072 TEST: 02                                                                                     TIME: 03:29:00       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01ES38042            ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 55947        
PATHOLOGIST: M. STEDHAM                                                                                        CAS: 509-14-8        
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Midwest Research Inst                                 TETRANITROMETHANE                                   DATE: 09/09/94      
EXPERIMENT: 05072 TEST: 02                                                                                     TIME: 03:29:00      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01ES38042            ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 55947       
PATHOLOGIST: M. STEDHAM                                                                                        CAS: 509-14-8       
 
 
 
 
 
                                                    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 Gland
                                                    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: Midwest Research Inst                                 TETRANITROMETHANE                                   DATE: 09/09/94       
EXPERIMENT: 05072 TEST: 02                                                                                     TIME: 03:29:00       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES38042            ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 55947        
PATHOLOGIST: M. STEDHAM                                                                                        CAS: 509-14-8        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                       IN THE ANALYSIS OF THE STUDY OF TETRANITROMETHANE
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             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
                             All Organs                    Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             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
                             Spleen                        Hemangiosarcoma
                             All Organs                    Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   1
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Gland: Non-medullary, Non-cortical                                                                                       |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/49 (4%)       0/50 (0%)      |     0/49 (0%)       0/49 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.7%            6.9%            0.0%          |      0.0%            0.0%            2.6%          |
|TERMINAL (d)           |     1/37 (3%)       1/25 (4%)       0/15 (0%)      |     0/31 (0%)       0/28 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         678             ---           |      ---             ---             666           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.498N        P=0.388         P=0.680N       |     P=0.334           (e)           P=0.539        |
|INCIDENTAL TUMOR       |     P=0.415N        P=0.410         P=0.680N       |     P=0.488           (e)           P=0.826        |
|LOGISTIC REGRESSION    |     P=0.407N        P=0.425         P=0.680N       |     P=0.316           (e)           P=0.507        |
|COCHRAN-ARMITAGE       |     P=0.302N                                       |     P=0.315                                        |
|FISHER EXACT           |                     P=0.492         P=0.500N       |                       (e)           P=0.505        |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.3%            3.8%            6.7%          |      3.2%            3.6%            0.0%          |
|TERMINAL (d)           |     1/37 (3%)       1/26 (4%)       1/15 (7%)      |     1/31 (3%)       1/28 (4%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      698             729 (T)         729 (T)       |      729 (T)         729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.643         P=0.620N        P=0.707        |     P=0.417N        P=0.739         P=0.551N       |
|INCIDENTAL TUMOR       |     P=0.665N        P=0.581N        P=0.672N       |     P=0.417N        P=0.739         P=0.551N       |
|LOGISTIC REGRESSION    |     P=0.667N        P=0.586N        P=0.689N       |     P=0.417N        P=0.739         P=0.551N       |
|COCHRAN-ARMITAGE       |     P=0.480N                                       |     P=0.364N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   2
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/49 (0%)       0/48 (0%)      |     3/49 (6%)       0/50 (0%)       0/49 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      8.9%            0.0%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       0/25 (0%)       0/15 (0%)      |     2/31 (6%)       0/28 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      627             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.133N        P=0.132N        P=0.149N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.194N        P=0.187N        P=0.238N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.117N        P=0.119N        P=0.123N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.115N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.117N        P=0.121N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       4/50 (8%)       1/50 (2%)      |     0/49 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      7.2%           10.9%            2.7%          |      0.0%            0.0%            4.2%          |
|TERMINAL (d)           |     1/37 (3%)       1/26 (4%)       0/15 (0%)      |     0/31 (0%)       0/28 (0%)       1/24 (4%)      |
|FIRST INCIDENCE (DAYS) |      504             580             588           |      ---             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.391N        P=0.381         P=0.478N       |     P=0.271           (e)           P=0.449        |
|INCIDENTAL TUMOR       |     P=0.059N        P=0.613N        P=0.094N       |     P=0.271           (e)           P=0.449        |
|LOGISTIC REGRESSION    |     P=0.164N        P=0.586         P=0.183N       |     P=0.271           (e)           P=0.449        |
|COCHRAN-ARMITAGE       |     P=0.206N                                       |     P=0.314                                        |
|FISHER EXACT           |                     P=0.500         P=0.309N       |                       (e)           P=0.505        |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   3
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    10/50 (20%)     15/50 (30%)      2/50 (4%)      |     9/49 (18%)      1/50 (2%)       4/50 (8%)      |
|ADJUSTED (b)           |     25.4%           44.2%            8.5%          |     23.4%            3.6%           14.7%          |
|TERMINAL (d)           |     8/37 (22%)      9/26 (35%)      0/15 (0%)      |     4/31 (13%)      1/28 (4%)       3/24 (13%)     |
|FIRST INCIDENCE (DAYS) |      674             566             671           |      563             729 (T)         645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.149N        P=0.043 *       P=0.208N       |     P=0.277N        P=0.014N*       P=0.174N       |
|INCIDENTAL TUMOR       |     P=0.021N*       P=0.118         P=0.085N       |     P=0.377N        P=0.022N*       P=0.246N       |
|LOGISTIC REGRESSION    |     P=0.017N*       P=0.112         P=0.076N       |     P=0.207N        P=0.009N**      P=0.110N       |
|COCHRAN-ARMITAGE       |     P=0.005N**                                     |     P=0.205N                                       |
|FISHER EXACT           |                     P=0.178         P=0.014N*      |                     P=0.007N**      P=0.109N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    13/50 (26%)     11/50 (22%)     11/50 (22%)     |     4/49 (8%)       2/50 (4%)       3/50 (6%)      |
|ADJUSTED (b)           |     30.7%           29.7%           41.0%          |     12.3%            7.1%           11.9%          |
|TERMINAL (d)           |     9/37 (24%)      4/26 (15%)      3/15 (20%)     |     3/31 (10%)      2/28 (7%)       2/24 (8%)      |
|FIRST INCIDENCE (DAYS) |      639             534             546           |      655             729 (T)         714           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.134         P=0.465         P=0.132        |     P=0.600         P=0.364N        P=0.601N       |
|INCIDENTAL TUMOR       |     P=0.280N        P=0.279N        P=0.379N       |     P=0.512N        P=0.279N        P=0.378N       |
|LOGISTIC REGRESSION    |     P=0.484N        P=0.409N        P=0.547N       |     P=0.558N        P=0.315N        P=0.505N       |
|COCHRAN-ARMITAGE       |     P=0.418N                                       |     P=0.532N                                       |
|FISHER EXACT           |                     P=0.408N        P=0.408N       |                     P=0.329N        P=0.489N       |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   4
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    23/50 (46%)     24/50 (48%)     12/50 (24%)     |    13/49 (27%)      3/50 (6%)       7/50 (14%)     |
|ADJUSTED (b)           |     52.9%           61.0%           43.5%          |     33.9%           10.7%           25.8%          |
|TERMINAL (d)           |    17/37 (46%)     12/26 (46%)      3/15 (20%)     |     7/31 (23%)      3/28 (11%)      5/24 (21%)     |
|FIRST INCIDENCE (DAYS) |      639             534             546           |      563             729 (T)         645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.553N        P=0.117         P=0.491        |     P=0.329N        P=0.011N*       P=0.193N       |
|INCIDENTAL TUMOR       |     P=0.010N*       P=0.495         P=0.045N*      |     P=0.330N        P=0.011N*       P=0.147N       |
|LOGISTIC REGRESSION    |     P=0.022N*       P=0.404         P=0.076N       |     P=0.216N        P=0.007N**      P=0.102N       |
|COCHRAN-ARMITAGE       |     P=0.007N**                                     |     P=0.208N                                       |
|FISHER EXACT           |                     P=0.500         P=0.018N*      |                     P=0.005N**      P=0.096N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    23/50 (46%)     24/50 (48%)     12/50 (24%)     |    13/49 (27%)      3/50 (6%)       7/50 (14%)     |
|ADJUSTED (b)           |     52.9%           61.0%           43.5%          |     33.9%           10.7%           25.8%          |
|TERMINAL (d)           |    17/37 (46%)     12/26 (46%)      3/15 (20%)     |     7/31 (23%)      3/28 (11%)      5/24 (21%)     |
|FIRST INCIDENCE (DAYS) |      639             534             546           |      563             729 (T)         645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.553N        P=0.117         P=0.491        |     P=0.329N        P=0.011N*       P=0.193N       |
|INCIDENTAL TUMOR       |     P=0.010N*       P=0.495         P=0.045N*      |     P=0.330N        P=0.011N*       P=0.147N       |
|LOGISTIC REGRESSION    |     P=0.022N*       P=0.404         P=0.076N       |     P=0.216N        P=0.007N**      P=0.102N       |
|COCHRAN-ARMITAGE       |     P=0.007N**                                     |     P=0.208N                                       |
|FISHER EXACT           |                     P=0.500         P=0.018N*      |                     P=0.005N**      P=0.096N       |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   5
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)     17/50 (34%)     34/50 (68%)     |     1/49 (2%)      19/50 (38%)     41/50 (82%)     |
|ADJUSTED (b)           |     17.5%           53.7%           90.5%          |      3.2%           56.6%           93.0%          |
|TERMINAL (d)           |     5/37 (14%)     12/26 (46%)     12/15 (80%)     |     1/31 (3%)      14/28 (50%)     21/24 (88%)     |
|FIRST INCIDENCE (DAYS) |      662             534             376           |      729 (T)         601             444           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.002 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P=0.003 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P=0.005 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.017 *       P<0.001 **     |                     P<0.001 **      P<0.001 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)     16/50 (32%)     46/50 (92%)     |     3/49 (6%)      11/50 (22%)     45/50 (90%)     |
|ADJUSTED (b)           |     15.7%           45.6%          100.0%          |      8.8%           34.2%           97.8%          |
|TERMINAL (d)           |     5/37 (14%)      8/26 (31%)     15/15 (100%)    |     2/31 (6%)       8/28 (29%)     23/24 (96%)     |
|FIRST INCIDENCE (DAYS) |      691             566             485           |      619             601             444           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.002 **      P<0.001 **     |     P<0.001 **      P=0.017 *       P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P=0.010 *       P<0.001 **     |     P<0.001 **      P=0.016 *       P<0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P=0.007 **      P<0.001 **     |     P<0.001 **      P=0.023 *       P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.014 *       P<0.001 **     |                     P=0.022 *       P<0.001 **     |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   6
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    12/50 (24%)     27/50 (54%)     47/50 (94%)     |     4/49 (8%)      24/50 (48%)     49/50 (98%)     |
|ADJUSTED (b)           |     29.7%           70.3%          100.0%          |     11.9%           69.7%          100.0%          |
|TERMINAL (d)           |     9/37 (24%)     15/26 (58%)     15/15 (100%)    |     3/31 (10%)     18/28 (64%)     24/24 (100%)    |
|FIRST INCIDENCE (DAYS) |      662             534             376           |      619             601             444           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P<0.001 **      P<0.001 **     |     P<0.001 **      P<0.001 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.002 **      P<0.001 **     |                     P<0.001 **      P<0.001 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/48 (0%)       0/48 (0%)       1/48 (2%)      |    18/49 (37%)     19/49 (39%)     14/48 (29%)     |
|ADJUSTED (b)           |      0.0%            0.0%            2.0%          |     51.0%           56.9%           48.1%          |
|TERMINAL (d)           |     0/37 (0%)       0/24 (0%)       0/14 (0%)      |    14/31 (45%)     14/28 (50%)      9/23 (39%)     |
|FIRST INCIDENCE (DAYS) |      ---             ---             145           |      590             592             674           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.315           (e)           P=0.500        |     P=0.484N        P=0.401         P=0.532N       |
|INCIDENTAL TUMOR       |     P=0.500           (e)             (e)          |     P=0.194N        P=0.569         P=0.219N       |
|LOGISTIC REGRESSION    |     P=0.260           (e)             (e)          |     P=0.219N        P=0.543         P=0.278N       |
|COCHRAN-ARMITAGE       |     P=0.311                                        |     P=0.216N                                       |
|FISHER EXACT           |                       (e)           P=0.500        |                     P=0.500         P=0.282N       |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   7
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/48 (0%)       0/48 (0%)       0/48 (0%)      |     2/49 (4%)       0/49 (0%)       0/48 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      4.6%            0.0%            0.0%          |
|TERMINAL (d)           |     0/37 (0%)       0/24 (0%)       0/14 (0%)      |     0/31 (0%)       0/28 (0%)       0/23 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      563             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.228N        P=0.245N        P=0.247N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.458N        P=0.444N        P=0.573N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.219N        P=0.183N        P=0.201N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.225N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.247N        P=0.253N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/48 (0%)       0/48 (0%)       1/48 (2%)      |    20/49 (41%)     19/49 (39%)     14/48 (29%)     |
|ADJUSTED (b)           |      0.0%            0.0%            2.0%          |     53.2%           56.9%           48.1%          |
|TERMINAL (d)           |     0/37 (0%)       0/24 (0%)       0/14 (0%)      |    14/31 (45%)     14/28 (50%)      9/23 (39%)     |
|FIRST INCIDENCE (DAYS) |      ---             ---             145           |      563             592             674           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.315           (e)           P=0.500        |     P=0.356N        P=0.559         P=0.373N       |
|INCIDENTAL TUMOR       |     P=0.500           (e)             (e)          |     P=0.150N        P=0.505N        P=0.172N       |
|LOGISTIC REGRESSION    |     P=0.260           (e)             (e)          |     P=0.132N        P=0.494N        P=0.159N       |
|COCHRAN-ARMITAGE       |     P=0.311                                        |     P=0.132N                                       |
|FISHER EXACT           |                       (e)           P=0.500        |                     P=0.500N        P=0.161N       |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   8
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            3.8%            0.0%          |      0.0%            0.0%            5.6%          |
|TERMINAL (d)           |     0/37 (0%)       1/26 (4%)       0/15 (0%)      |     0/31 (0%)       0/28 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             729 (T)         ---           |      ---             ---             673           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.827N        P=0.430           (e)          |     P=0.097           (e)           P=0.262        |
|INCIDENTAL TUMOR       |     P=0.827N        P=0.430           (e)          |     P=0.240           (e)           P=0.643        |
|LOGISTIC REGRESSION    |     P=0.827N        P=0.430           (e)          |     P=0.092           (e)           P=0.238        |
|COCHRAN-ARMITAGE       |     P=0.689N                                       |     P=0.092                                        |
|FISHER EXACT           |                     P=0.500           (e)          |                       (e)           P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            3.8%            0.0%          |      0.0%            0.0%            5.6%          |
|TERMINAL (d)           |     0/37 (0%)       1/26 (4%)       0/15 (0%)      |     0/31 (0%)       0/28 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             729 (T)         ---           |      ---             ---             673           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.827N        P=0.430           (e)          |     P=0.097           (e)           P=0.262        |
|INCIDENTAL TUMOR       |     P=0.827N        P=0.430           (e)          |     P=0.240           (e)           P=0.643        |
|LOGISTIC REGRESSION    |     P=0.827N        P=0.430           (e)          |     P=0.092           (e)           P=0.238        |
|COCHRAN-ARMITAGE       |     P=0.689N                                       |     P=0.092                                        |
|FISHER EXACT           |                     P=0.500           (e)          |                       (e)           P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE   9
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       3/49 (6%)       1/50 (2%)      |     0/48 (0%)       0/49 (0%)       4/50 (8%)      |
|ADJUSTED (b)           |      4.6%           10.0%            6.7%          |      0.0%            0.0%           14.7%          |
|TERMINAL (d)           |     0/37 (0%)       2/26 (8%)       1/15 (7%)      |     0/31 (0%)       0/28 (0%)       3/24 (13%)     |
|FIRST INCIDENCE (DAYS) |      629             622             729 (T)       |      ---             ---             666           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.622N        P=0.370         P=0.719N       |     P=0.006 **        (e)           P=0.047 *      |
|INCIDENTAL TUMOR       |     P=0.319N        P=0.681         P=0.380N       |     P=0.011 *         (e)           P=0.071        |
|LOGISTIC REGRESSION    |     P=0.411N        P=0.494         P=0.547N       |     P=0.009 **        (e)           P=0.061        |
|COCHRAN-ARMITAGE       |     P=0.354N                                       |     P=0.011 *                                      |
|FISHER EXACT           |                     P=0.490         P=0.500N       |                       (e)           P=0.064        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/48 (0%)       1/50 (2%)      |     3/48 (6%)       2/50 (4%)       3/50 (6%)      |
|ADJUSTED (b)           |      4.8%            0.0%            5.3%          |      9.6%            6.9%           12.5%          |
|TERMINAL (d)           |     1/37 (3%)       0/26 (0%)       0/15 (0%)      |     2/30 (7%)       1/28 (4%)       3/24 (13%)     |
|FIRST INCIDENCE (DAYS) |      646             ---             717           |      704             718             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.669         P=0.310N        P=0.730N       |     P=0.468         P=0.525N        P=0.561        |
|INCIDENTAL TUMOR       |     P=0.589N        P=0.278N        P=0.539N       |     P=0.628         P=0.294N        P=0.650N       |
|LOGISTIC REGRESSION    |     P=0.641N        P=0.224N        P=0.594N       |     P=0.546         P=0.462N        P=0.650        |
|COCHRAN-ARMITAGE       |     P=0.564N                                       |     P=0.586                                        |
|FISHER EXACT           |                     P=0.258N        P=0.500N       |                     P=0.480N        P=0.641N       |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE  10
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |                                                    |      6.2%            2.6%            2.9%          |
|TERMINAL (d)           |                                                    |     1/31 (3%)       0/28 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      657             692             684           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.492N        P=0.470N        P=0.500N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.230N        P=0.219N        P=0.189N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.480N        P=0.499N        P=0.500N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.480N                                       |
|FISHER EXACT           |                                                    |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     1/50 (2%)       3/50 (6%)       1/50 (2%)      |
|ADJUSTED (b)           |                                                    |      3.2%            9.5%            4.2%          |
|TERMINAL (d)           |                                                    |     1/31 (3%)       2/28 (7%)       1/24 (4%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      729 (T)         665             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.582N        P=0.298         P=0.704        |
|INCIDENTAL TUMOR       |                                                    |     P=0.508N        P=0.384         P=0.704        |
|LOGISTIC REGRESSION    |                                                    |     P=0.527N        P=0.317         P=0.704        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.518N                                       |
|FISHER EXACT           |                                                    |                     P=0.309         P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE  11
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       7/50 (14%)      2/50 (4%)      |     3/50 (6%)       2/50 (4%)       6/50 (12%)     |
|ADJUSTED (b)           |      9.1%           21.6%            9.2%          |      9.3%            5.1%           21.1%          |
|TERMINAL (d)           |     1/37 (3%)       4/26 (15%)      1/15 (7%)      |     2/31 (6%)       0/28 (0%)       4/24 (17%)     |
|FIRST INCIDENCE (DAYS) |      504             580             588           |      657             665             666           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.500N        P=0.145         P=0.594N       |     P=0.101         P=0.466N        P=0.190        |
|INCIDENTAL TUMOR       |     P=0.103N        P=0.427         P=0.103N       |     P=0.263         P=0.186N        P=0.392        |
|LOGISTIC REGRESSION    |     P=0.180N        P=0.295         P=0.235N       |     P=0.125         P=0.498N        P=0.239        |
|COCHRAN-ARMITAGE       |     P=0.189N                                       |     P=0.128                                        |
|FISHER EXACT           |                     P=0.262         P=0.339N       |                     P=0.500N        P=0.243        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      7/50 (14%)      2/50 (4%)      |     3/50 (6%)       3/50 (6%)       6/50 (12%)     |
|ADJUSTED (b)           |     11.6%           21.6%            9.2%          |      9.3%            8.5%           21.1%          |
|TERMINAL (d)           |     2/37 (5%)       4/26 (15%)      1/15 (7%)      |     2/31 (6%)       1/28 (4%)       4/24 (17%)     |
|FIRST INCIDENCE (DAYS) |      504             580             588           |      657             665             666           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.423N        P=0.219         P=0.497N       |     P=0.127         P=0.639N        P=0.190        |
|INCIDENTAL TUMOR       |     P=0.077N        P=0.537         P=0.077N       |     P=0.303         P=0.381N        P=0.392        |
|LOGISTIC REGRESSION    |     P=0.129N        P=0.409         P=0.156N       |     P=0.160         P=0.659N        P=0.239        |
|COCHRAN-ARMITAGE       |     P=0.130N                                       |     P=0.165                                        |
|FISHER EXACT           |                     P=0.380         P=0.218N       |                     P=0.661N        P=0.243        |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE  12
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.4%            2.1%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/37 (5%)       0/26 (0%)       0/15 (0%)      |     0/31 (0%)       0/28 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         426             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.310N        P=0.586N        P=0.452N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.161N        P=0.504N        P=0.452N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.163N        P=0.420N        P=0.452N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.195N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       5/50 (10%)      2/50 (4%)      |    11/50 (22%)     13/50 (26%)     15/50 (30%)     |
|ADJUSTED (b)           |     10.8%           13.2%           11.6%          |     29.9%           33.4%           40.6%          |
|TERMINAL (d)           |     4/37 (11%)      0/26 (0%)       1/15 (7%)      |     7/31 (23%)      4/28 (14%)      6/24 (25%)     |
|FIRST INCIDENCE (DAYS) |      729 (T)         426             717           |      480             263             444           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.571N        P=0.344         P=0.603        |     P=0.168         P=0.394         P=0.185        |
|INCIDENTAL TUMOR       |     P=0.222N        P=0.543         P=0.674N       |     P=0.428         P=0.549N        P=0.212        |
|LOGISTIC REGRESSION    |     P=0.262N        P=0.543         P=0.677N       |     P=0.237         P=0.408         P=0.247        |
|COCHRAN-ARMITAGE       |     P=0.240N                                       |     P=0.238                                        |
|FISHER EXACT           |                     P=0.500         P=0.339N       |                     P=0.408         P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE  13
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       4/50 (8%)       2/50 (4%)      |    11/50 (22%)     13/50 (26%)     15/50 (30%)     |
|ADJUSTED (b)           |      5.4%           11.4%           11.6%          |     29.9%           33.4%           40.6%          |
|TERMINAL (d)           |     2/37 (5%)       0/26 (0%)       1/15 (7%)      |     7/31 (23%)      4/28 (14%)      6/24 (25%)     |
|FIRST INCIDENCE (DAYS) |      729 (T)         643             717           |      480             263             444           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.433         P=0.227         P=0.372        |     P=0.168         P=0.394         P=0.185        |
|INCIDENTAL TUMOR       |     P=0.512N        P=0.382         P=0.470        |     P=0.428         P=0.549N        P=0.212        |
|LOGISTIC REGRESSION    |     P=0.627N        P=0.323         P=0.437        |     P=0.237         P=0.408         P=0.247        |
|COCHRAN-ARMITAGE       |     P=0.514N                                       |     P=0.238                                        |
|FISHER EXACT           |                     P=0.339         P=0.691N       |                     P=0.408         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    20/50 (40%)     26/50 (52%)     37/50 (74%)     |    29/50 (58%)     36/50 (72%)     45/50 (90%)     |
|ADJUSTED (b)           |     46.2%           70.9%           91.6%          |     70.2%           92.2%           97.8%          |
|TERMINAL (d)           |    14/37 (38%)     16/26 (62%)     12/15 (80%)     |    19/31 (61%)     25/28 (89%)     23/24 (96%)     |
|FIRST INCIDENCE (DAYS) |      646             534             145           |      544             592             444           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.016 *       P<0.001 **     |     P<0.001 **      P=0.086         P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P=0.066         P=0.001 **     |     P<0.001 **      P=0.141         P=0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P=0.073         P<0.001 **     |     P<0.001 **      P=0.093         P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.158         P<0.001 **     |                     P=0.104         P<0.001 **     |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE  14
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         0.5 PPM         2 PPM         |      CONTROL         0.5 PPM         2 PPM         |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    25/50 (50%)     31/50 (62%)     46/50 (92%)     |    22/50 (44%)     24/50 (48%)     47/50 (94%)     |
|ADJUSTED (b)           |     54.9%           66.9%          100.0%          |     52.7%           56.0%          100.0%          |
|TERMINAL (d)           |    17/37 (46%)     11/26 (42%)     15/15 (100%)    |    12/31 (39%)     10/28 (36%)     24/24 (100%)    |
|FIRST INCIDENCE (DAYS) |      504             426             485           |      480             263             444           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.026 *       P<0.001 **     |     P<0.001 **      P=0.408         P<0.001 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P=0.365         P<0.001 **     |     P<0.001 **      P=0.527N        P<0.001 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P=0.169         P<0.001 **     |     P<0.001 **      P=0.420         P<0.001 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.157         P<0.001 **     |                     P=0.421         P<0.001 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    39/50 (78%)     40/50 (80%)     48/50 (96%)     |    40/50 (80%)     44/50 (88%)     49/50 (98%)     |
|ADJUSTED (b)           |     81.2%           85.1%          100.0%          |     85.0%           97.7%          100.0%          |
|TERMINAL (d)           |    28/37 (76%)     19/26 (73%)     15/15 (100%)    |    24/31 (77%)     27/28 (96%)     24/24 (100%)    |
|FIRST INCIDENCE (DAYS) |      504             426             145           |      480             263             444           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.039 *       P<0.001 **     |     P=0.012 *       P=0.216         P=0.022 *      |
|INCIDENTAL TUMOR       |     P=0.011 *       P=0.513         P=0.018 *      |     P=0.010 **      P=0.169         P=0.007 **     |
|LOGISTIC REGRESSION    |     P=0.002 **      P=0.351         P=0.004 **     |     P=0.004 **      P=0.162         P=0.003 **     |
|COCHRAN-ARMITAGE       |     P=0.006 **                                     |     P=0.005 **                                     |
|FISHER EXACT           |                     P=0.500         P=0.007 **     |                     P=0.207         P=0.004 **     |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05072 TEST: 02                                                 PAGE  15
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- TETRANITROMETHANE
 
                                                 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).