National Toxicology Program

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TDMS Study 05130-02 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Microbiological Assoc.                               C. I. DIRECT BLUE 218                                DATE: 09/17/94       
EXPERIMENT: 05130 TEST: 02                                                                                     TIME: 00:05:08       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-5096           ROUTE: DOSED FEED                                                                  NTP C#: 60877B       
PATHOLOGIST: L. BRENNECKE                                                                                      CAS: 10401-500       
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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: Microbiological Assoc.                               C. I. DIRECT BLUE 218                                DATE: 09/17/94      
EXPERIMENT: 05130 TEST: 02                                                                                     TIME: 00:05:08      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NO1-ES-5096           ROUTE: DOSED FEED                                                                  NTP C#: 60877B      
PATHOLOGIST: L. BRENNECKE                                                                                      CAS: 10401-500      
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    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: Microbiological Assoc.                               C. I. DIRECT BLUE 218                                DATE: 09/17/94       
EXPERIMENT: 05130 TEST: 02                                                                                     TIME: 00:05:08       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-5096           ROUTE: DOSED FEED                                                                  NTP C#: 60877B       
PATHOLOGIST: L. BRENNECKE                                                                                      CAS: 10401-500       
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                     IN THE ANALYSIS OF THE STUDY OF C. I. DIRECT BLUE 218
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Harderian Gland               Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatoblastoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             All Organs                    Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatoblastoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             All Organs                    Hemangiosarcoma
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   1
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    3/50 (6%)    1/50 (2%)    0/50 (0%)  |  0/49 (0%)    0/49 (0%)    0/48 (0%)    1/48 (2%)  |
|ADJUSTED (b)           |   0.0%         6.5%         2.4%         0.0%      |   0.0%         0.0%         0.0%         2.7%      |
|TERMINAL (d)           |  0/44 (0%)    3/46 (7%)    1/42 (2%)    0/45 (0%)  |  0/37 (0%)    0/40 (0%)    0/46 (0%)    1/37 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          737 (T)      737 (T)      ---       |   ---          ---          ---          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.280N     P=0.129      P=0.491        (e)      |  P=0.208        (e)          (e)        P=0.500    |
|INCIDENTAL TUMOR       |  P=0.280N     P=0.129      P=0.491        (e)      |  P=0.208        (e)          (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.280N     P=0.129      P=0.491        (e)      |  P=0.208        (e)          (e)        P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.280N                                          |  P=0.218                                           |
|FISHER EXACT           |               P=0.121      P=0.500        (e)      |                 (e)          (e)        P=0.495    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)  |  0/49 (0%)    1/49 (2%)    2/48 (4%)    0/47 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         2.5%         4.3%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/46 (0%)    0/42 (0%)    0/45 (0%)  |  0/37 (0%)    1/40 (3%)    2/46 (4%)    0/36 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          739 (T)      739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.522N     P=0.516      P=0.288        (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.522N     P=0.516      P=0.288        (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.522N     P=0.516      P=0.288        (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.512N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.500      P=0.242        (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   2
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    4/50 (8%)    4/50 (8%)    0/50 (0%)  |  3/49 (6%)    0/50 (0%)    2/49 (4%)    0/49 (0%)  |
|ADJUSTED (b)           |   6.6%         8.7%         9.2%         0.0%      |   8.1%         0.0%         4.3%         0.0%      |
|TERMINAL (d)           |  2/44 (5%)    4/46 (9%)    3/42 (7%)    0/45 (0%)  |  3/37 (8%)    0/40 (0%)    2/46 (4%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   613          737 (T)      686          ---       |   739 (T)      ---          739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.067N     P=0.524      P=0.487      P=0.119N   |  P=0.175N     P=0.108N     P=0.401N     P=0.116N   |
|INCIDENTAL TUMOR       |  P=0.047N*    P=0.358      P=0.560      P=0.082N   |  P=0.175N     P=0.108N     P=0.401N     P=0.116N   |
|LOGISTIC REGRESSION    |  P=0.065N     P=0.504      P=0.497      P=0.127N   |  P=0.175N     P=0.108N     P=0.401N     P=0.115N   |
|COCHRAN-ARMITAGE       |  P=0.066N                                          |  P=0.178N                                          |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.121N   |               P=0.117N     P=0.500N     P=0.121N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    1/50 (2%)    0/50 (0%)    3/50 (6%)  |  0/49 (0%)    0/50 (0%)    1/49 (2%)    1/49 (2%)  |
|ADJUSTED (b)           |   2.3%         2.2%         0.0%         6.7%      |   0.0%         0.0%         2.2%         2.6%      |
|TERMINAL (d)           |  1/44 (2%)    1/46 (2%)    0/42 (0%)    3/45 (7%)  |  0/37 (0%)    0/40 (0%)    1/46 (2%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      737 (T)      ---          737 (T)   |   ---          ---          739 (T)      739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.127      P=0.752N     P=0.509N     P=0.314    |  P=0.316        (e)        P=0.543      P=0.505    |
|INCIDENTAL TUMOR       |  P=0.127      P=0.752N     P=0.509N     P=0.314    |  P=0.316        (e)        P=0.543      P=0.505    |
|LOGISTIC REGRESSION    |  P=0.127      P=0.752N     P=0.509N     P=0.314    |  P=0.316        (e)        P=0.543      P=0.505    |
|COCHRAN-ARMITAGE       |  P=0.123                                           |  P=0.323                                           |
|FISHER EXACT           |               P=0.753N     P=0.500N     P=0.309    |                 (e)        P=0.500      P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   3
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    0/50 (0%)    0/50 (0%)    3/50 (6%)  |  0/49 (0%)    0/50 (0%)    1/49 (2%)    0/49 (0%)  |
|ADJUSTED (b)           |   2.3%         0.0%         0.0%         6.7%      |   0.0%         0.0%         2.2%         0.0%      |
|TERMINAL (d)           |  1/44 (2%)    0/46 (0%)    0/42 (0%)    3/45 (7%)  |  0/37 (0%)    0/40 (0%)    1/46 (2%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      ---          ---          737 (T)   |   ---          ---          739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.055      P=0.491N     P=0.509N     P=0.314    |  P=0.788N       (e)        P=0.543        (e)      |
|INCIDENTAL TUMOR       |  P=0.055      P=0.491N     P=0.509N     P=0.314    |  P=0.788N       (e)        P=0.543        (e)      |
|LOGISTIC REGRESSION    |  P=0.055      P=0.491N     P=0.509N     P=0.314    |  P=0.788N       (e)        P=0.543        (e)      |
|COCHRAN-ARMITAGE       |  P=0.053                                           |  P=0.781N                                          |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.309    |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    2/50 (4%)    1/50 (2%)    1/50 (2%)  |  0/49 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)  |
|ADJUSTED (b)           |   0.0%         4.3%         2.4%         2.2%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    2/46 (4%)    1/42 (2%)    1/45 (2%)  |  0/37 (0%)    0/40 (0%)    0/46 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          737 (T)      737 (T)      737 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.628      P=0.248      P=0.491      P=0.504    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.628      P=0.248      P=0.491      P=0.504    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.628      P=0.248      P=0.491      P=0.504    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.627                                           |    (e)                                             |
|FISHER EXACT           |               P=0.247      P=0.500      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   4
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    3/50 (6%)    1/50 (2%)    1/50 (2%)  |  0/49 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)  |
|ADJUSTED (b)           |   0.0%         6.5%         2.4%         2.2%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    3/46 (7%)    1/42 (2%)    1/45 (2%)  |  0/37 (0%)    0/40 (0%)    0/46 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          737 (T)      737 (T)      737 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.588N     P=0.129      P=0.491      P=0.504    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.588N     P=0.129      P=0.491      P=0.504    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.588N     P=0.129      P=0.491      P=0.504    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.592N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.121      P=0.500      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    1/50 (2%)    1/50 (2%)  |  1/49 (2%)    3/50 (6%)    0/49 (0%)    1/49 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.1%         2.1%      |   2.2%         7.5%         0.0%         2.6%      |
|TERMINAL (d)           |  0/44 (0%)    0/46 (0%)    0/42 (0%)    0/45 (0%)  |  0/37 (0%)    3/40 (8%)    0/46 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          646          660       |   580          739 (T)      ---          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.332        (e)        P=0.508      P=0.508    |  P=0.465N     P=0.334      P=0.487N     P=0.758    |
|INCIDENTAL TUMOR       |  P=0.321        (e)        P=0.718      P=0.581    |  P=0.561N     P=0.307        (e)        P=0.609    |
|LOGISTIC REGRESSION    |  P=0.271        (e)        P=0.461      P=0.464    |  P=0.457N     P=0.307      P=0.616N     P=0.763N   |
|COCHRAN-ARMITAGE       |  P=0.325                                           |  P=0.457N                                          |
|FISHER EXACT           |                 (e)        P=0.500      P=0.500    |               P=0.316      P=0.500N     P=0.753N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   5
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/50 (32%)  19/50 (38%)  17/50 (34%)  40/50 (80%) |  7/49 (14%)  12/50 (24%)  17/49 (35%)  41/49 (84%) |
|ADJUSTED (b)           |  34.7%        40.4%        38.6%        81.6%      |  18.4%        30.0%        36.1%        91.1%      |
|TERMINAL (d)           | 14/44 (32%)  18/46 (39%)  15/42 (36%)  36/45 (80%) |  6/37 (16%)  12/40 (30%)  16/46 (35%)  34/38 (89%) |
|FIRST INCIDENCE (DAYS) |   519          689          686          576       |   701          739 (T)      676          541       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.401      P=0.447      P<0.001 ** |  P<0.001 **   P=0.198      P=0.066      P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.306      P=0.499      P<0.001 ** |  P<0.001 **   P=0.215      P=0.047 *    P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.371      P=0.526      P<0.001 ** |  P<0.001 **   P=0.185      P=0.041 *    P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.338      P=0.500      P<0.001 ** |               P=0.166      P=0.017 *    P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/50 (14%)   3/50 (6%)    8/50 (16%)  17/50 (34%) |  5/49 (10%)   5/50 (10%)   6/49 (12%)  12/49 (24%) |
|ADJUSTED (b)           |  15.9%         6.5%        17.1%        36.0%      |  13.5%        12.0%        13.0%        30.6%      |
|TERMINAL (d)           |  7/44 (16%)   3/46 (7%)    4/42 (10%)  15/45 (33%) |  5/37 (14%)   4/40 (10%)   6/46 (13%)  11/38 (29%) |
|FIRST INCIDENCE (DAYS) |   737 (T)      737 (T)      622          568       |   739 (T)      648          739 (T)      689       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.141N     P=0.479      P=0.022 *  |  P=0.012 *    P=0.578N     P=0.603N     P=0.061    |
|INCIDENTAL TUMOR       |  P=0.001 **   P=0.141N     P=0.585N     P=0.027 *  |  P=0.014 *    P=0.553N     P=0.603N     P=0.067    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.141N     P=0.506      P=0.019 *  |  P=0.012 *    P=0.586N     P=0.603N     P=0.061    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.014 *                                         |
|FISHER EXACT           |               P=0.159N     P=0.500      P=0.017 *  |               P=0.617N     P=0.500      P=0.054    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   6
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/50 (14%)   3/50 (6%)    8/50 (16%)  17/50 (34%) |  5/49 (10%)   5/50 (10%)   6/49 (12%)  13/49 (27%) |
|ADJUSTED (b)           |  15.9%         6.5%        17.1%        36.0%      |  13.5%        12.0%        13.0%        33.2%      |
|TERMINAL (d)           |  7/44 (16%)   3/46 (7%)    4/42 (10%)  15/45 (33%) |  5/37 (14%)   4/40 (10%)   6/46 (13%)  12/38 (32%) |
|FIRST INCIDENCE (DAYS) |   737 (T)      737 (T)      622          568       |   739 (T)      648          739 (T)      689       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.141N     P=0.479      P=0.022 *  |  P=0.005 **   P=0.578N     P=0.603N     P=0.038 *  |
|INCIDENTAL TUMOR       |  P=0.001 **   P=0.141N     P=0.585N     P=0.027 *  |  P=0.006 **   P=0.553N     P=0.603N     P=0.042 *  |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.141N     P=0.506      P=0.019 *  |  P=0.005 **   P=0.586N     P=0.603N     P=0.038 *  |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.006 **                                        |
|FISHER EXACT           |               P=0.159N     P=0.500      P=0.017 *  |               P=0.617N     P=0.500      P=0.033 *  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 21/50 (42%)  20/50 (40%)  23/50 (46%)  45/50 (90%) | 10/49 (20%)  15/50 (30%)  21/49 (43%)  45/49 (92%) |
|ADJUSTED (b)           |  45.5%        42.6%        48.8%        90.0%      |  26.3%        36.4%        44.7%       100.0%      |
|TERMINAL (d)           | 19/44 (43%)  19/46 (41%)  18/42 (43%)  40/45 (89%) |  9/37 (24%)  14/40 (35%)  20/46 (43%)  38/38 (100%)|
|FIRST INCIDENCE (DAYS) |   519          689          622          568       |   701          648          676          541       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.428N     P=0.369      P<0.001 ** |  P<0.001 **   P=0.239      P=0.072      P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.523N     P=0.484      P<0.001 ** |  P<0.001 **   P=0.269      P=0.054      P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.451N     P=0.446      P<0.001 ** |  P<0.001 **   P=0.226      P=0.045 *    P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.500N     P=0.420      P<0.001 ** |               P=0.193      P=0.014 *    P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   7
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 21/50 (42%)  20/50 (40%)  23/50 (46%)  45/50 (90%) | 10/49 (20%)  15/50 (30%)  21/49 (43%)  45/49 (92%) |
|ADJUSTED (b)           |  45.5%        42.6%        48.8%        90.0%      |  26.3%        36.4%        44.7%       100.0%      |
|TERMINAL (d)           | 19/44 (43%)  19/46 (41%)  18/42 (43%)  40/45 (89%) |  9/37 (24%)  14/40 (35%)  20/46 (43%)  38/38 (100%)|
|FIRST INCIDENCE (DAYS) |   519          689          622          568       |   701          648          676          541       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.428N     P=0.369      P<0.001 ** |  P<0.001 **   P=0.239      P=0.072      P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.523N     P=0.484      P<0.001 ** |  P<0.001 **   P=0.269      P=0.054      P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.451N     P=0.446      P<0.001 ** |  P<0.001 **   P=0.226      P=0.045 *    P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.500N     P=0.420      P<0.001 ** |               P=0.193      P=0.014 *    P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/50 (26%)   9/50 (18%)   7/50 (14%)   4/50 (8%)  |  5/49 (10%)   7/50 (14%)   4/49 (8%)    1/49 (2%)  |
|ADJUSTED (b)           |  28.2%        19.6%        16.7%         8.9%      |  13.5%        17.5%         8.7%         2.6%      |
|TERMINAL (d)           | 11/44 (25%)   9/46 (20%)   7/42 (17%)   4/45 (9%)  |  5/37 (14%)   7/40 (18%)   4/46 (9%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   613          737 (T)      737 (T)      737 (T)   |   739 (T)      739 (T)      739 (T)      739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.020N*    P=0.204N     P=0.128N     P=0.016N*  |  P=0.038N*    P=0.434      P=0.365N     P=0.096N   |
|INCIDENTAL TUMOR       |  P=0.015N*    P=0.259N     P=0.103N     P=0.011N*  |  P=0.038N*    P=0.434      P=0.365N     P=0.096N   |
|LOGISTIC REGRESSION    |  P=0.018N*    P=0.208N     P=0.096N     P=0.014N*  |  P=0.038N*    P=0.434      P=0.365N     P=0.096N   |
|COCHRAN-ARMITAGE       |  P=0.020N*                                         |  P=0.041N*                                         |
|FISHER EXACT           |               P=0.235N     P=0.105N     P=0.016N*  |               P=0.394      P=0.500N     P=0.102N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   8
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    3/50 (6%)    2/50 (4%)    1/50 (2%)  |  0/49 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)  |
|ADJUSTED (b)           |   2.3%         6.5%         4.7%         2.2%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/44 (2%)    3/46 (7%)    1/42 (2%)    1/45 (2%)  |  0/37 (0%)    0/40 (0%)    0/46 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      737 (T)      704          737 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.418N     P=0.321      P=0.487      P=0.757N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.413N     P=0.321      P=0.608      P=0.757N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.414N     P=0.321      P=0.506      P=0.757N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.422N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.309      P=0.500      P=0.753N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/50 (28%)  12/50 (24%)   9/50 (18%)   5/50 (10%) |  5/49 (10%)   7/50 (14%)   4/49 (8%)    1/49 (2%)  |
|ADJUSTED (b)           |  30.4%        26.1%        20.9%        11.1%      |  13.5%        17.5%         8.7%         2.6%      |
|TERMINAL (d)           | 12/44 (27%)  12/46 (26%)   8/42 (19%)   5/45 (11%) |  5/37 (14%)   7/40 (18%)   4/46 (9%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   613          737 (T)      704          737 (T)   |   739 (T)      739 (T)      739 (T)      739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.016N*    P=0.362N     P=0.205N     P=0.020N*  |  P=0.038N*    P=0.434      P=0.365N     P=0.096N   |
|INCIDENTAL TUMOR       |  P=0.012N*    P=0.433N     P=0.141N     P=0.014N*  |  P=0.038N*    P=0.434      P=0.365N     P=0.096N   |
|LOGISTIC REGRESSION    |  P=0.014N*    P=0.369N     P=0.157N     P=0.017N*  |  P=0.038N*    P=0.434      P=0.365N     P=0.096N   |
|COCHRAN-ARMITAGE       |  P=0.016N*                                         |  P=0.041N*                                         |
|FISHER EXACT           |               P=0.410N     P=0.171N     P=0.020N*  |               P=0.394      P=0.500N     P=0.102N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE   9
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/47 (4%)    1/50 (2%)    0/48 (0%)    1/49 (2%)  |
|ADJUSTED (b)           |                                                    |   5.4%         2.5%         0.0%         2.6%      |
|TERMINAL (d)           |                                                    |  2/37 (5%)    1/40 (3%)    0/46 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   739 (T)      739 (T)      ---          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.534N     P=0.473N     P=0.192N     P=0.491N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.534N     P=0.473N     P=0.192N     P=0.491N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.534N     P=0.473N     P=0.192N     P=0.491N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.520N                                          |
|FISHER EXACT           |                                                    |               P=0.477N     P=0.242N     P=0.484N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Granulosa Cell Tumor Benign                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/47 (0%)    1/50 (2%)    2/48 (4%)    0/49 (0%)  |
|ADJUSTED (b)           |                                                    |   0.0%         2.5%         4.3%         0.0%      |
|TERMINAL (d)           |                                                    |  0/37 (0%)    1/40 (3%)    2/46 (4%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          739 (T)      739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.506N     P=0.516      P=0.288        (e)      |
|INCIDENTAL TUMOR       |                                                    |  P=0.506N     P=0.516      P=0.288        (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.506N     P=0.516      P=0.288        (e)      |
|COCHRAN-ARMITAGE       |                                                    |  P=0.495N                                          |
|FISHER EXACT           |                                                    |               P=0.515      P=0.253        (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE  10
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/49 (0%)    0/48 (0%)    0/48 (0%)    0/48 (0%)  |  2/48 (4%)    6/50 (12%)   2/49 (4%)    0/45 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   5.6%        15.0%         4.3%         0.0%      |
|TERMINAL (d)           |  0/43 (0%)    0/44 (0%)    0/41 (0%)    0/43 (0%)  |  2/36 (6%)    6/40 (15%)   2/46 (4%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   739 (T)      739 (T)      739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.056N     P=0.169      P=0.604N     P=0.244N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.056N     P=0.169      P=0.604N     P=0.244N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.056N     P=0.169      P=0.604N     P=0.244N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.061N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.148      P=0.684N     P=0.264N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)  |  0/49 (0%)    2/50 (4%)    0/49 (0%)    0/49 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.4%         0.0%      |   0.0%         4.9%         0.0%         0.0%      |
|TERMINAL (d)           |  0/44 (0%)    0/46 (0%)    1/42 (2%)    0/45 (0%)  |  0/37 (0%)    1/40 (3%)    0/46 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          737 (T)      ---       |   ---          693          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.776N       (e)        P=0.491        (e)      |  P=0.389N     P=0.254        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.776N       (e)        P=0.491        (e)      |  P=0.361N     P=0.305        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.776N       (e)        P=0.491        (e)      |  P=0.396N     P=0.249        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.779N                                          |  P=0.394N                                          |
|FISHER EXACT           |                 (e)        P=0.500        (e)      |               P=0.253        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE  11
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    2/50 (4%)    0/50 (0%)    2/50 (4%)  |  0/49 (0%)    1/50 (2%)    0/49 (0%)    1/49 (2%)  |
|ADJUSTED (b)           |   4.5%         4.3%         0.0%         4.4%      |   0.0%         2.5%         0.0%         2.6%      |
|TERMINAL (d)           |  2/44 (5%)    2/46 (4%)    0/42 (0%)    2/45 (4%)  |  0/37 (0%)    1/40 (3%)    0/46 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      737 (T)      ---          737 (T)   |   ---          739 (T)      ---          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.607      P=0.679N     P=0.249N     P=0.686N   |  P=0.458      P=0.516        (e)        P=0.505    |
|INCIDENTAL TUMOR       |  P=0.607      P=0.679N     P=0.249N     P=0.686N   |  P=0.458      P=0.516        (e)        P=0.505    |
|LOGISTIC REGRESSION    |  P=0.607      P=0.679N     P=0.249N     P=0.686N   |  P=0.458      P=0.516        (e)        P=0.505    |
|COCHRAN-ARMITAGE       |  P=0.605                                           |  P=0.462                                           |
|FISHER EXACT           |               P=0.691N     P=0.247N     P=0.691N   |               P=0.505        (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/50 (4%)    2/50 (4%)    0/50 (0%)    2/50 (4%)  |  0/49 (0%)    2/50 (4%)    0/49 (0%)    1/49 (2%)  |
|ADJUSTED (b)           |   4.5%         4.3%         0.0%         4.4%      |   0.0%         4.5%         0.0%         2.6%      |
|TERMINAL (d)           |  2/44 (5%)    2/46 (4%)    0/42 (0%)    2/45 (4%)  |  0/37 (0%)    1/40 (3%)    0/46 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      737 (T)      ---          737 (T)   |   ---          554          ---          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.607      P=0.679N     P=0.249N     P=0.686N   |  P=0.610      P=0.258        (e)        P=0.505    |
|INCIDENTAL TUMOR       |  P=0.607      P=0.679N     P=0.249N     P=0.686N   |  P=0.489      P=0.223        (e)        P=0.505    |
|LOGISTIC REGRESSION    |  P=0.607      P=0.679N     P=0.249N     P=0.686N   |  P=0.626      P=0.191        (e)        P=0.505    |
|COCHRAN-ARMITAGE       |  P=0.605                                           |  P=0.615                                           |
|FISHER EXACT           |               P=0.691N     P=0.247N     P=0.691N   |               P=0.253        (e)        P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE  12
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/49 (2%)    1/50 (2%)    2/49 (4%)    1/49 (2%)  |
|ADJUSTED (b)           |                                                    |   2.5%         2.5%         4.3%         2.6%      |
|TERMINAL (d)           |                                                    |  0/37 (0%)    1/40 (3%)    2/46 (4%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   688          739 (T)      739 (T)      739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.641N     P=0.749N     P=0.569      P=0.749N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.617N     P=0.695N     P=0.504      P=0.702N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.645N     P=0.753N     P=0.521      P=0.761N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.639N                                          |
|FISHER EXACT           |                                                    |               P=0.747N     P=0.500      P=0.753N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)  |  1/49 (2%)    0/50 (0%)    1/49 (2%)    2/49 (4%)  |
|ADJUSTED (b)           |   0.0%         2.2%         0.0%         4.4%      |   2.4%         0.0%         2.2%         5.3%      |
|TERMINAL (d)           |  0/44 (0%)    1/46 (2%)    0/42 (0%)    2/45 (4%)  |  0/37 (0%)    0/40 (0%)    1/46 (2%)    2/38 (5%)  |
|FIRST INCIDENCE (DAYS) |   ---          737 (T)      ---          737 (T)   |   627          ---          739 (T)      739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.152      P=0.509        (e)        P=0.243    |  P=0.228      P=0.478N     P=0.721N     P=0.509    |
|INCIDENTAL TUMOR       |  P=0.152      P=0.509        (e)        P=0.243    |  P=0.141      P=0.545N     P=0.543      P=0.344    |
|LOGISTIC REGRESSION    |  P=0.152      P=0.509        (e)        P=0.243    |  P=0.234      P=0.548N     P=0.747      P=0.501    |
|COCHRAN-ARMITAGE       |  P=0.149                                           |  P=0.236                                           |
|FISHER EXACT           |               P=0.500        (e)        P=0.247    |               P=0.495N     P=0.753N     P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE  13
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    1/50 (2%)    2/50 (4%)    2/50 (4%)  |  1/49 (2%)    6/50 (12%)   0/49 (0%)    2/49 (4%)  |
|ADJUSTED (b)           |   2.3%         2.1%         4.4%         4.2%      |   2.2%        14.0%         0.0%         5.3%      |
|TERMINAL (d)           |  1/44 (2%)    0/46 (0%)    1/42 (2%)    0/45 (0%)  |  0/37 (0%)    4/40 (10%)   0/46 (0%)    2/38 (5%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      659          646          660       |   580          522          ---          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.406      P=0.751N     P=0.494      P=0.512    |  P=0.442N     P=0.077      P=0.487N     P=0.501    |
|INCIDENTAL TUMOR       |  P=0.409      P=0.711N     P=0.608      P=0.604    |  P=0.444N     P=0.059        (e)        P=0.344    |
|LOGISTIC REGRESSION    |  P=0.351      P=0.755      P=0.494      P=0.472    |  P=0.425N     P=0.046 *    P=0.616N     P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.395                                           |  P=0.434N                                          |
|FISHER EXACT           |               P=0.753N     P=0.500      P=0.500    |               P=0.059      P=0.500N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/50 (2%)    2/50 (4%)    2/50 (4%)    4/50 (8%)  |  2/49 (4%)    6/50 (12%)   1/49 (2%)    4/49 (8%)  |
|ADJUSTED (b)           |   2.3%         4.2%         4.4%         8.4%      |   4.6%        14.0%         2.2%        10.5%      |
|TERMINAL (d)           |  1/44 (2%)    1/46 (2%)    1/42 (2%)    2/45 (4%)  |  0/37 (0%)    4/40 (10%)   1/46 (2%)    4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   737 (T)      659          646          660       |   580          522          739 (T)      739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.138      P=0.515      P=0.494      P=0.193    |  P=0.485      P=0.169      P=0.452N     P=0.346    |
|INCIDENTAL TUMOR       |  P=0.123      P=0.557      P=0.608      P=0.227    |  P=0.423      P=0.123      P=0.543      P=0.147    |
|LOGISTIC REGRESSION    |  P=0.111      P=0.494      P=0.494      P=0.170    |  P=0.502      P=0.106      P=0.594N     P=0.337    |
|COCHRAN-ARMITAGE       |  P=0.128                                           |  P=0.495                                           |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.181    |               P=0.141      P=0.500N     P=0.339    |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE  14
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/50 (6%)    4/50 (8%)    2/50 (4%)    3/50 (6%)  |  7/49 (14%)  12/50 (24%)   8/49 (16%)   5/49 (10%) |
|ADJUSTED (b)           |   6.7%         8.4%         4.8%         6.7%      |  17.5%        26.0%        16.6%        12.7%      |
|TERMINAL (d)           |  2/44 (5%)    3/46 (7%)    2/42 (5%)    3/45 (7%)  |  5/37 (14%)   7/40 (18%)   6/46 (13%)   4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   676          455          737 (T)      737 (T)   |   518          554          532          694       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.539N     P=0.523      P=0.517N     P=0.651N   |  P=0.148N     P=0.221      P=0.559N     P=0.362N   |
|INCIDENTAL TUMOR       |  P=0.602      P=0.497      P=0.425N     P=0.622N   |  P=0.177N     P=0.164      P=0.421      P=0.390N   |
|LOGISTIC REGRESSION    |  P=0.567N     P=0.455      P=0.492N     P=0.651N   |  P=0.133N     P=0.142      P=0.467      P=0.376N   |
|COCHRAN-ARMITAGE       |  P=0.546N                                          |  P=0.137N                                          |
|FISHER EXACT           |               P=0.500      P=0.500N     P=0.661N   |               P=0.166      P=0.500      P=0.380N   |
|=================================================================================================================================|
|                                                                                                                                 |
|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%)    2/50 (4%)  |  7/49 (14%)  11/50 (22%)   8/49 (16%)   5/49 (10%) |
|ADJUSTED (b)           |   4.4%         8.4%         4.8%         4.4%      |  17.5%        24.5%        16.6%        12.7%      |
|TERMINAL (d)           |  1/44 (2%)    3/46 (7%)    2/42 (5%)    2/45 (4%)  |  5/37 (14%)   7/40 (18%)   6/46 (13%)   4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   676          455          737 (T)      737 (T)   |   518          590          532          694       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.446N     P=0.360      P=0.681      P=0.685N   |  P=0.172N     P=0.289      P=0.559N     P=0.362N   |
|INCIDENTAL TUMOR       |  P=0.526N     P=0.331      P=0.617N     P=0.651N   |  P=0.181N     P=0.243      P=0.421      P=0.390N   |
|LOGISTIC REGRESSION    |  P=0.478N     P=0.285      P=0.690N     P=0.691N   |  P=0.162N     P=0.221      P=0.467      P=0.376N   |
|COCHRAN-ARMITAGE       |  P=0.450N                                          |  P=0.163N                                          |
|FISHER EXACT           |               P=0.339      P=0.691N     P=0.691N   |               P=0.232      P=0.500      P=0.380N   |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE  15
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 25/50 (50%)  31/50 (62%)  21/50 (42%)  42/50 (84%) | 20/49 (41%)  21/50 (42%)  26/49 (53%)  42/49 (86%) |
|ADJUSTED (b)           |  53.1%        66.0%        47.7%        85.7%      |  49.7%        52.5%        55.3%        91.3%      |
|TERMINAL (d)           | 22/44 (50%)  30/46 (65%)  19/42 (45%)  38/45 (84%) | 17/37 (46%)  21/40 (53%)  25/46 (54%)  34/38 (89%) |
|FIRST INCIDENCE (DAYS) |   519          689          686          576       |   184          739 (T)      676          108       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.231      P=0.344N     P=0.002 ** |  P<0.001 **   P=0.536N     P=0.485      P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.167      P=0.261N     P<0.001 ** |  P<0.001 **   P=0.553      P=0.273      P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.202      P=0.240N     P<0.001 ** |  P<0.001 **   P=0.548      P=0.221      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.157      P=0.274N     P<0.001 ** |               P=0.534      P=0.156      P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/50 (28%)  15/50 (30%)  12/50 (24%)  24/50 (48%) | 14/49 (29%)  24/50 (48%)  17/49 (35%)  24/49 (49%) |
|ADJUSTED (b)           |  31.1%        30.0%        25.4%        48.9%      |  33.6%        48.9%        34.7%        55.6%      |
|TERMINAL (d)           | 13/44 (30%)  11/46 (24%)   7/42 (17%)  20/45 (44%) | 10/37 (27%)  15/40 (38%)  14/46 (30%)  19/38 (50%) |
|FIRST INCIDENCE (DAYS) |   676          455          622          568       |   518          522          532          108       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.018 *    P=0.555      P=0.450N     P=0.047 *  |  P=0.102      P=0.086      P=0.576N     P=0.052    |
|INCIDENTAL TUMOR       |  P=0.016 *    P=0.589      P=0.238N     P=0.064    |  P=0.088      P=0.049 *    P=0.273      P=0.038 *  |
|LOGISTIC REGRESSION    |  P=0.013 *    P=0.504      P=0.392N     P=0.036 *  |  P=0.067      P=0.033 *    P=0.339      P=0.031 *  |
|COCHRAN-ARMITAGE       |  P=0.010 *                                         |  P=0.090                                           |
|FISHER EXACT           |               P=0.500      P=0.410N     P=0.032 *  |               P=0.037 *    P=0.332      P=0.031 *  |
|=================================================================================================================================|
 
         DATE: 09/17/94                     EXPERIMENT: 05130 TEST: 02                                                 PAGE  16
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- C. I. DIRECT BLUE 218
 
                                                 TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      1000 PPM     3000 PPM     10000PPM  |   CONTROL      1000 PPM     3000 PPM     10000PPM  |
|                       |   MALE         LOW MALE     MID MALE     HIGHMALE  |   FEMALE       LOW FEM      MID FEM      HIGH FEM  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 31/50 (62%)  37/50 (74%)  28/50 (56%)  46/50 (92%) | 29/49 (59%)  35/50 (70%)  34/49 (69%)  46/49 (94%) |
|ADJUSTED (b)           |  65.9%        74.0%        59.5%        92.0%      |  65.6%        71.4%        69.4%       100.0%      |
|TERMINAL (d)           | 28/44 (64%)  33/46 (72%)  23/42 (55%)  41/45 (91%) | 22/37 (59%)  26/40 (65%)  31/46 (67%)  38/38 (100%)|
|FIRST INCIDENCE (DAYS) |   519          455          622          568       |   184          522          532          108       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.003 **   P=0.251      P=0.434N     P=0.004 ** |  P<0.001 **   P=0.335      P=0.472N     P=0.002 ** |
|INCIDENTAL TUMOR       |  P=0.001 **   P=0.167      P=0.269N     P=0.001 ** |  P<0.001 **   P=0.216      P=0.209      P<0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.173      P=0.295N     P<0.001 ** |  P<0.001 **   P=0.185      P=0.232      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.142      P=0.342N     P<0.001 ** |               P=0.180      P=0.200      P<0.001 ** |
|=================================================================================================================================|
 
 (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).
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.