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TDMS Study 05075-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                     DIPHENYLHYDANTOIN                                   DATE: 09/09/94       
EXPERIMENT: 05075 TEST: 01                                                                                     TIME: 09:34:49       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-82151          ROUTE: DOSED FEED                                                                  NTP C#: 55765        
PATHOLOGIST: M. RYAN                         S. EUSTIS                                                         CAS: 57-41-0         
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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: Battelle Columbus                                     DIPHENYLHYDANTOIN                                   DATE: 09/09/94      
EXPERIMENT: 05075 TEST: 01                                                                                     TIME: 09:34:49      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NO1-ES-82151          ROUTE: DOSED FEED                                                                  NTP C#: 55765       
PATHOLOGIST: M. RYAN                         S. EUSTIS                                                         CAS: 57-41-0        
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                     DIPHENYLHYDANTOIN                                   DATE: 09/09/94       
EXPERIMENT: 05075 TEST: 01                                                                                     TIME: 09:34:49       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-82151          ROUTE: DOSED FEED                                                                  NTP C#: 55765        
PATHOLOGIST: M. RYAN                         S. EUSTIS                                                         CAS: 57-41-0         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                       IN THE ANALYSIS OF THE STUDY OF DIPHENYLHYDANTOIN
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Cortex                Adenoma
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Clitoral/Preputial Gland      Carcinoma or Adenoma
                             Islets, Pancreatic            Adenoma
                                                           Carcinoma or Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Carcinoma
                             Mammary Gland                 Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Skin: Subcutaneous Tissue     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                             Testes                        Adenoma
                             Thyroid Gland: C-Cell         Carcinoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                     DIPHENYLHYDANTOIN                                   DATE: 09/09/94       
EXPERIMENT: 05075 TEST: 01                                                                                     TIME: 09:34:49       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-82151          ROUTE: DOSED FEED                                                                  NTP C#: 55765        
PATHOLOGIST: M. RYAN                         S. EUSTIS                                                         CAS: 57-41-0         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                       IN THE ANALYSIS OF THE STUDY OF DIPHENYLHYDANTOIN
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma or Adenoma
                             Mammary Gland                 Carcinoma
                                                           Carcinoma or Adenoma
                                                           Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Thyroid Gland: C-Cell         Adenoma
                                                           Carcinoma or Adenoma
                             Uterus                        Polyp Stromal
                                                           Sarcoma Stromal or Polyp Stromal
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   1
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/48 (0%)    0/145 (0%)   3/99 (3%)  |  2/71 (3%)    0/23 (0%)    0/50 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         5.2%      |   6.3%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/32 (0%)    0/70 (0%)    1/52 (2%)  |  2/32 (6%)    0/0          0/0          0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          697       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.012 *      (e)          (e)        P=0.137    |  P=0.057N       (e)          (e)        P=0.093N   |
|INCIDENTAL TUMOR       |  P=0.009 **     (e)          (e)        P=0.108    |  P=0.057N       (e)          (e)        P=0.093N   |
|LOGISTIC REGRESSION    |  P=0.010 *      (e)          (e)        P=0.124    |  P=0.057N       (e)          (e)        P=0.093N   |
|COCHRAN-ARMITAGE       |  P=0.011 *                                         |  P=0.152N                                          |
|FISHER EXACT           |                 (e)          (e)        P=0.121    |               P=0.569N     P=0.342N     P=0.171N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 31/100 (31%) 16/50 (32%)  56/146 (38%) 52/98 (53%) |  5/70 (7%)    0/23 (0%)    2/52 (4%)    5/100 (5%) |
|ADJUSTED (b)           |  47.7%        43.9%        56.7%        69.5%      |  12.1%         0.0%        50.4%         6.9%      |
|TERMINAL (d)           | 18/50 (36%)  13/33 (39%)  32/71 (45%)  30/52 (58%) |  3/31 (10%)   0/0          1/2 (50%)    3/69 (4%)  |
|FIRST INCIDENCE (DAYS) |   627          549          501          494       |   627          ---          648          671       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.001 **   P=0.281N     P=0.164      P=0.009 ** |  P=0.300N     P=0.413N     P=0.678N     P=0.317N   |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.574N     P=0.144      P<0.001 ** |  P=0.396N     P=0.326N     P=0.673      P=0.444N   |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.501N     P=0.155      P<0.001 ** |  P=0.344N     P=0.316N     P=0.606N     P=0.330N   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.538N                                          |
|FISHER EXACT           |               P=0.522      P=0.147      P=0.001 ** |               P=0.233N     P=0.359N     P=0.394N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   2
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   2/50 (4%)    7/146 (5%)   3/98 (3%)  |  1/70 (1%)    0/23 (0%)    0/52 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   1.2%         4.3%         7.2%         4.6%      |   3.2%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    2/71 (3%)    1/52 (2%)  |  1/31 (3%)    0/0          0/2 (0%)     0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   632          340          307          399       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.450      P=0.273      P=0.109      P=0.320    |  P=0.224N       (e)        P=0.967N     P=0.341N   |
|INCIDENTAL TUMOR       |  P=0.430      P=0.601      P=0.148      P=0.297    |  P=0.224N       (e)        P=0.967N     P=0.341N   |
|LOGISTIC REGRESSION    |  P=0.529      P=0.413      P=0.111      P=0.345    |  P=0.224N       (e)        P=0.967N     P=0.341N   |
|COCHRAN-ARMITAGE       |  P=0.442                                           |  P=0.362N                                          |
|FISHER EXACT           |               P=0.258      P=0.096      P=0.303    |               P=0.753N     P=0.574N     P=0.412N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/100 (32%) 18/50 (36%)  62/146 (42%) 54/98 (55%) |  6/70 (9%)    0/23 (0%)    2/52 (4%)    5/100 (5%) |
|ADJUSTED (b)           |  48.4%        46.3%        60.5%        71.1%      |  15.2%         0.0%        50.4%         6.9%      |
|TERMINAL (d)           | 18/50 (36%)  13/33 (39%)  34/71 (48%)  31/52 (60%) |  4/31 (13%)   0/0          1/2 (50%)    3/69 (4%)  |
|FIRST INCIDENCE (DAYS) |   627          340          307          399       |   627          ---          648          671       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002 **   P=0.409N     P=0.084      P=0.007 ** |  P=0.170N     P=0.413N     P=0.652N     P=0.183N   |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.528      P=0.076      P<0.001 ** |  P=0.237N     P=0.326N     P=0.692      P=0.278N   |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.427      P=0.065      P<0.001 ** |  P=0.216N     P=0.287N     P=0.536N     P=0.199N   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P=0.411N                                          |
|FISHER EXACT           |               P=0.377      P=0.063      P<0.001 ** |               P=0.172N     P=0.255N     P=0.267N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   3
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    2/150 (1%)   1/100 (1%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         1.8%         1.2%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          652          609       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.392        (e)        P=0.339      P=0.495    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.378        (e)        P=0.355      P=0.485    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.416        (e)        P=0.338      P=0.537    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.397                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.359      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/77 (3%)    0/17 (0%)    0/82 (0%)    1/100 (1%) |  0/71 (0%)    0/23 (0%)    0/52 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   3.2%         0.0%         0.0%         1.7%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/27 (0%)    0/0          0/3 (0%)     0/53 (0%)  |  0/31 (0%)    0/0          0/1 (0%)     0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   662          ---          ---          715       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.601N     P=0.359N     P=0.160N     P=0.483N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.622N     P=0.547N     P=0.136N     P=0.552N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.401N     P=0.678N     P=0.265N     P=0.388N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.462N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.669N     P=0.233N     P=0.403N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   4
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/76 (4%)    1/18 (6%)    3/86 (3%)    2/99 (2%)  |  4/66 (6%)    4/24 (17%)   6/58 (10%)   1/99 (1%)  |
|ADJUSTED (b)           |   6.6%        50.0%        14.2%         3.8%      |  12.9%       100.0%        31.5%         1.5%      |
|TERMINAL (d)           |  1/26 (4%)    1/2 (50%)    1/8 (13%)    2/53 (4%)  |  4/31 (13%)   1/1 (100%)   3/10 (30%)   1/68 (1%)  |
|FIRST INCIDENCE (DAYS) |   613          732 (T)      626          732 (T)   |   729 (T)      634          439          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.159N     P=0.682      P=0.632      P=0.311N   |  P=0.003N**   P=0.004 **   P=0.071      P=0.028N*  |
|INCIDENTAL TUMOR       |  P=0.167N     P=0.595      P=0.636      P=0.341N   |  P=0.004N**   P=0.019 *    P=0.063      P=0.028N*  |
|LOGISTIC REGRESSION    |  P=0.192N     P=0.568      P=0.654N     P=0.347N   |  P=0.012N*    P=0.030 *    P=0.270      P=0.028N*  |
|COCHRAN-ARMITAGE       |  P=0.273N                                          |  P=0.014N*                                         |
|FISHER EXACT           |               P=0.579      P=0.599N     P=0.377N   |               P=0.128      P=0.293      P=0.084N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/76 (4%)    0/18 (0%)    2/86 (2%)    0/99 (0%)  |  2/66 (3%)    0/24 (0%)    1/58 (2%)    2/99 (2%)  |
|ADJUSTED (b)           |   6.3%         0.0%        13.2%         0.0%      |   4.7%         0.0%        10.0%         2.8%      |
|TERMINAL (d)           |  1/26 (4%)    0/2 (0%)     1/8 (13%)    0/53 (0%)  |  1/31 (3%)    0/1 (0%)     1/10 (10%)   1/68 (1%)  |
|FIRST INCIDENCE (DAYS) |   634          ---          623          ---       |   700          ---          729 (T)      693       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.063N     P=0.361N     P=0.587N     P=0.085N   |  P=0.463N     P=0.624N     P=0.696N     P=0.533N   |
|INCIDENTAL TUMOR       |  P=0.065N     P=0.441N     P=0.588N     P=0.098N   |  P=0.541N     P=0.597N     P=0.724N     P=0.663N   |
|LOGISTIC REGRESSION    |  P=0.071N     P=0.481N     P=0.473N     P=0.080N   |  P=0.434N     P=0.669N     P=0.729      P=0.498N   |
|COCHRAN-ARMITAGE       |  P=0.077N                                          |  P=0.592N                                          |
|FISHER EXACT           |               P=0.524N     P=0.442N     P=0.080N   |               P=0.536N     P=0.549N     P=0.526N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   5
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/76 (8%)    1/18 (6%)    5/86 (6%)    2/99 (2%)  |  6/66 (9%)    4/24 (17%)   7/58 (12%)   3/99 (3%)  |
|ADJUSTED (b)           |  12.6%        50.0%        27.1%         3.8%      |  17.4%       100.0%        41.2%         4.2%      |
|TERMINAL (d)           |  2/26 (8%)    1/2 (50%)    2/8 (25%)    2/53 (4%)  |  5/31 (16%)   1/1 (100%)   4/10 (40%)   2/68 (3%)  |
|FIRST INCIDENCE (DAYS) |   613          732 (T)      623          732 (T)   |   700          634          439          693       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.026N*    P=0.455N     P=0.589N     P=0.053N   |  P=0.004N**   P=0.023 *    P=0.108      P=0.044N*  |
|INCIDENTAL TUMOR       |  P=0.027N*    P=0.595N     P=0.589N     P=0.066N   |  P=0.006N**   P=0.070      P=0.091      P=0.067N   |
|LOGISTIC REGRESSION    |  P=0.037N*    P=0.647N     P=0.473N     P=0.062N   |  P=0.016N*    P=0.075      P=0.334      P=0.046N*  |
|COCHRAN-ARMITAGE       |  P=0.058N                                          |  P=0.023N*                                         |
|FISHER EXACT           |               P=0.598N     P=0.414N     P=0.070N   |               P=0.255      P=0.401      P=0.093N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Ear                                                                                                                              |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |  0/100 (0%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         1.9%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    1/99 (1%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          699          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.634N       (e)        P=0.352        (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.712N       (e)        P=0.310        (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.658N       (e)        P=0.340        (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.664N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.359        (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   6
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/77 (5%)    0/15 (0%)    1/76 (1%)    0/97 (0%)  |  2/70 (3%)    1/23 (4%)    1/48 (2%)    0/100 (0%) |
|ADJUSTED (b)           |   9.9%         0.0%         0.9%         0.0%      |   4.4%         0.0%         1.0%         0.0%      |
|TERMINAL (d)           |  2/27 (7%)    0/0          0/3 (0%)     0/52 (0%)  |  1/31 (3%)    0/0          0/1 (0%)     0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   543          ---          652          ---       |   652          681          711          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.027N*    P=0.382N     P=0.293N     P=0.030N*  |  P=0.083N     P=0.588      P=0.635N     P=0.156N   |
|INCIDENTAL TUMOR       |  P=0.025N*    P=0.755N     P=0.345N     P=0.033N*  |  P=0.130N     P=0.600      P=0.711N     P=0.206N   |
|LOGISTIC REGRESSION    |  P=0.036N*    P=0.438N     P=0.199N     P=0.039N*  |  P=0.064N     P=0.581      P=0.717      P=0.156N   |
|COCHRAN-ARMITAGE       |  P=0.038N*                                         |  P=0.087N                                          |
|FISHER EXACT           |               P=0.484N     P=0.187N     P=0.037N*  |               P=0.578      P=0.639N     P=0.168N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/77 (1%)    0/15 (0%)    2/76 (3%)    0/97 (0%)  |  0/70 (0%)    0/23 (0%)    0/48 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   3.7%         0.0%        33.8%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/27 (4%)    0/0          1/3 (33%)    0/52 (0%)  |  0/31 (0%)    0/0          0/1 (0%)     0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          517          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.188N       (e)        P=0.136      P=0.369N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.172N       (e)        P=0.098      P=0.369N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.292N       (e)        P=0.491      P=0.369N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.291N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.837N     P=0.495      P=0.443N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   7
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/77 (6%)    0/15 (0%)    3/76 (4%)    0/97 (0%)  |  2/70 (3%)    1/23 (4%)    1/48 (2%)    0/100 (0%) |
|ADJUSTED (b)           |  13.5%         0.0%        34.4%         0.0%      |   4.4%         0.0%         1.0%         0.0%      |
|TERMINAL (d)           |  3/27 (11%)   0/0          1/3 (33%)    0/52 (0%)  |  1/31 (3%)    0/0          0/1 (0%)     0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   543          ---          517          ---       |   652          681          711          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.010N**   P=0.382N     P=0.607      P=0.011N*  |  P=0.083N     P=0.588      P=0.635N     P=0.156N   |
|INCIDENTAL TUMOR       |  P=0.008N**   P=0.755N     P=0.514      P=0.012N*  |  P=0.130N     P=0.600      P=0.711N     P=0.206N   |
|LOGISTIC REGRESSION    |  P=0.020N*    P=0.395N     P=0.384N     P=0.017N*  |  P=0.064N     P=0.581      P=0.717      P=0.156N   |
|COCHRAN-ARMITAGE       |  P=0.021N*                                         |  P=0.087N                                          |
|FISHER EXACT           |               P=0.402N     P=0.367N     P=0.016N*  |               P=0.578      P=0.639N     P=0.168N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Pelvis and Transitional Epithelium                                                                                       |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/78 (0%)    0/21 (0%)    2/89 (2%)    0/100 (0%) |  0/71 (0%)    0/23 (0%)    0/52 (0%)    0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         1.5%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/28 (0%)    0/4 (0%)     0/11 (0%)    0/53 (0%)  |  0/31 (0%)    0/0          0/2 (0%)     0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          487          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.671N       (e)        P=0.333        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.612N       (e)        P=0.295        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.560N       (e)        P=0.350        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.558N                                          |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.283        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   8
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   2/49 (4%)    4/148 (3%)   9/99 (9%)  |  0/99 (0%)    0/50 (0%)    2/150 (1%)   1/100 (1%) |
|ADJUSTED (b)           |   1.4%         5.7%         5.6%        15.4%      |   0.0%         0.0%         2.0%         1.4%      |
|TERMINAL (d)           |  0/50 (0%)    1/33 (3%)    4/71 (6%)    5/53 (9%)  |  0/60 (0%)    0/27 (0%)    2/99 (2%)    1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   662          683          732 (T)      695       |   ---          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.004 **   P=0.327      P=0.308      P=0.017 *  |  P=0.439        (e)        P=0.355      P=0.528    |
|INCIDENTAL TUMOR       |  P=0.003 **   P=0.187      P=0.313      P=0.009 ** |  P=0.439        (e)        P=0.355      P=0.528    |
|LOGISTIC REGRESSION    |  P=0.003 **   P=0.264      P=0.325      P=0.012 *  |  P=0.439        (e)        P=0.355      P=0.528    |
|COCHRAN-ARMITAGE       |  P=0.003 **                                        |  P=0.398                                           |
|FISHER EXACT           |               P=0.252      P=0.329      P=0.009 ** |                 (e)        P=0.362      P=0.503    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   3/49 (6%)    5/148 (3%)   9/99 (9%)  |  0/99 (0%)    0/50 (0%)    2/150 (1%)   1/100 (1%) |
|ADJUSTED (b)           |   1.4%         8.4%         7.0%        15.4%      |   0.0%         0.0%         2.0%         1.4%      |
|TERMINAL (d)           |  0/50 (0%)    1/33 (3%)    5/71 (7%)    5/53 (9%)  |  0/60 (0%)    0/27 (0%)    2/99 (2%)    1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   662          683          732 (T)      695       |   ---          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.011 *    P=0.159      P=0.210      P=0.017 *  |  P=0.439        (e)        P=0.355      P=0.528    |
|INCIDENTAL TUMOR       |  P=0.008 **   P=0.043 *    P=0.213      P=0.009 ** |  P=0.439        (e)        P=0.355      P=0.528    |
|LOGISTIC REGRESSION    |  P=0.009 **   P=0.107      P=0.226      P=0.012 *  |  P=0.439        (e)        P=0.355      P=0.528    |
|COCHRAN-ARMITAGE       |  P=0.010 **                                        |  P=0.398                                           |
|FISHER EXACT           |               P=0.104      P=0.225      P=0.009 ** |                 (e)        P=0.362      P=0.503    |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE   9
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   3/49 (6%)    5/148 (3%)   9/99 (9%)  |  0/99 (0%)    0/50 (0%)    2/150 (1%)   1/100 (1%) |
|ADJUSTED (b)           |   1.4%         8.4%         7.0%        15.4%      |   0.0%         0.0%         2.0%         1.4%      |
|TERMINAL (d)           |  0/50 (0%)    1/33 (3%)    5/71 (7%)    5/53 (9%)  |  0/60 (0%)    0/27 (0%)    2/99 (2%)    1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   662          683          732 (T)      695       |   ---          ---          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.011 *    P=0.159      P=0.210      P=0.017 *  |  P=0.439        (e)        P=0.355      P=0.528    |
|INCIDENTAL TUMOR       |  P=0.008 **   P=0.043 *    P=0.213      P=0.009 ** |  P=0.439        (e)        P=0.355      P=0.528    |
|LOGISTIC REGRESSION    |  P=0.009 **   P=0.107      P=0.226      P=0.012 *  |  P=0.439        (e)        P=0.355      P=0.528    |
|COCHRAN-ARMITAGE       |  P=0.010 **                                        |  P=0.398                                           |
|FISHER EXACT           |               P=0.104      P=0.225      P=0.009 ** |                 (e)        P=0.362      P=0.503    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/77 (3%)    0/18 (0%)    1/83 (1%)    2/100 (2%) |  1/72 (1%)    0/24 (0%)    0/54 (0%)    1/100 (1%) |
|ADJUSTED (b)           |   5.4%         0.0%         1.1%         3.4%      |   3.1%         0.0%         0.0%         1.4%      |
|TERMINAL (d)           |  1/27 (4%)    0/1 (0%)     0/4 (0%)     1/53 (2%)  |  1/32 (3%)    0/1 (0%)     0/3 (0%)     1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   715          ---          694          695       |   729 (T)      ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.590N     P=0.561N     P=0.587N     P=0.556N   |  P=0.499N     P=0.997N     P=0.931N     P=0.581N   |
|INCIDENTAL TUMOR       |  P=0.607N     P=0.709N     P=0.565N     P=0.602N   |  P=0.499N     P=0.997N     P=0.931N     P=0.581N   |
|LOGISTIC REGRESSION    |  P=0.490N     P=0.788N     P=0.656N     P=0.517N   |  P=0.499N     P=0.997N     P=0.931N     P=0.581N   |
|COCHRAN-ARMITAGE       |  P=0.638                                           |  P=0.684                                           |
|FISHER EXACT           |               P=0.655N     P=0.472N     P=0.586N   |               P=0.750N     P=0.571N     P=0.663N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  10
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/77 (1%)    1/18 (6%)    0/83 (0%)    4/100 (4%) |  1/72 (1%)    0/24 (0%)    1/54 (2%)    0/100 (0%) |
|ADJUSTED (b)           |   3.7%       100.0%         0.0%         7.5%      |   3.1%         0.0%         1.0%         0.0%      |
|TERMINAL (d)           |  1/27 (4%)    1/1 (100%)   0/4 (0%)     4/53 (8%)  |  1/32 (3%)    0/1 (0%)     0/3 (0%)     0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      732 (T)      ---          732 (T)   |   729 (T)      ---          704          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.527      P=0.048 *    P=0.866N     P=0.428    |  P=0.248N     P=0.997N     P=0.644      P=0.347N   |
|INCIDENTAL TUMOR       |  P=0.527      P=0.048 *    P=0.866N     P=0.428    |  P=0.299N     P=0.997N     P=0.582      P=0.347N   |
|LOGISTIC REGRESSION    |  P=0.527      P=0.048 *    P=0.866N     P=0.428    |  P=0.220N     P=0.997N     P=0.476      P=0.347N   |
|COCHRAN-ARMITAGE       |  P=0.170                                           |  P=0.316N                                          |
|FISHER EXACT           |               P=0.345      P=0.481N     P=0.276    |               P=0.750N     P=0.675      P=0.419N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/77 (4%)    1/18 (6%)    1/83 (1%)    6/100 (6%) |  2/72 (3%)    0/24 (0%)    1/54 (2%)    1/100 (1%) |
|ADJUSTED (b)           |   9.1%       100.0%         1.1%        10.8%      |   6.3%         0.0%         1.0%         1.4%      |
|TERMINAL (d)           |  2/27 (7%)    1/1 (100%)   0/4 (0%)     5/53 (9%)  |  2/32 (6%)    0/1 (0%)     0/3 (0%)     1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   715          732 (T)      694          695       |   729 (T)      ---          704          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.555      P=0.494      P=0.520N     P=0.550    |  P=0.200N     P=0.967N     P=0.681      P=0.245N   |
|INCIDENTAL TUMOR       |  P=0.546      P=0.366      P=0.498N     P=0.518    |  P=0.230N     P=0.967N     P=0.627      P=0.245N   |
|LOGISTIC REGRESSION    |  P=0.559      P=0.354      P=0.513N     P=0.567    |  P=0.196N     P=0.967N     P=0.566      P=0.245N   |
|COCHRAN-ARMITAGE       |  P=0.237                                           |  P=0.383N                                          |
|FISHER EXACT           |               P=0.575      P=0.282N     P=0.393    |               P=0.561N     P=0.607N     P=0.378N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  11
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |  2/100 (2%)   0/50 (0%)    1/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   3.3%         0.0%         1.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  2/60 (3%)    0/27 (0%)    1/99 (1%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   729 (T)      ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.196N     P=0.426N     P=0.330N     P=0.209N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.196N     P=0.426N     P=0.330N     P=0.209N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.196N     P=0.426N     P=0.330N     P=0.209N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.223N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.443N     P=0.351N     P=0.249N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |  6/100 (6%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   2.0%         0.0%         0.0%         0.0%      |   8.1%         0.0%         2.0%         0.0%      |
|TERMINAL (d)           |  1/50 (2%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  2/60 (3%)    0/27 (0%)    1/99 (1%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          ---          ---       |   388          ---          711          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.445N     P=0.583N     P=0.430N     P=0.488N   |  P=0.020N*    P=0.108N     P=0.039N*    P=0.017N*  |
|INCIDENTAL TUMOR       |  P=0.445N     P=0.583N     P=0.430N     P=0.488N   |  P=0.039N*    P=0.102N     P=0.068N     P=0.043N*  |
|LOGISTIC REGRESSION    |  P=0.445N     P=0.583N     P=0.430N     P=0.488N   |  P=0.022N*    P=0.099N     P=0.050N     P=0.017N*  |
|COCHRAN-ARMITAGE       |  P=0.443N                                          |  P=0.024N*                                         |
|FISHER EXACT           |               P=0.667N     P=0.400N     P=0.500N   |               P=0.083N     P=0.047N*    P=0.014N*  |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  12
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |  8/100 (8%)   0/50 (0%)    3/150 (2%)   0/100 (0%) |
|ADJUSTED (b)           |   2.0%         0.0%         0.0%         0.0%      |  11.3%         0.0%         3.0%         0.0%      |
|TERMINAL (d)           |  1/50 (2%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  4/60 (7%)    0/27 (0%)    2/99 (2%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          ---          ---       |   388          ---          711          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.445N     P=0.583N     P=0.430N     P=0.488N   |  P=0.007N**   P=0.060N     P=0.020N*    P=0.004N** |
|INCIDENTAL TUMOR       |  P=0.445N     P=0.583N     P=0.430N     P=0.488N   |  P=0.013N*    P=0.056N     P=0.034N*    P=0.012N*  |
|LOGISTIC REGRESSION    |  P=0.445N     P=0.583N     P=0.430N     P=0.488N   |  P=0.009N**   P=0.049N*    P=0.026N*    P=0.006N** |
|COCHRAN-ARMITAGE       |  P=0.443N                                          |  P=0.009N**                                        |
|FISHER EXACT           |               P=0.667N     P=0.400N     P=0.500N   |               P=0.035N*    P=0.026N*    P=0.003N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/100 (4%)   4/50 (8%)    2/150 (1%)   1/100 (1%) | 26/100 (26%) 14/50 (28%)  18/150 (12%)  6/100 (6%) |
|ADJUSTED (b)           |   6.4%        10.9%         2.1%         1.9%      |  34.7%        41.2%        16.2%         8.0%      |
|TERMINAL (d)           |  2/50 (4%)    2/33 (6%)    1/71 (1%)    1/53 (2%)  | 14/60 (23%)   8/27 (30%)  12/99 (12%)   3/69 (4%)  |
|FIRST INCIDENCE (DAYS) |   617          654          597          732 (T)   |   586          630          595          630       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.071N     P=0.359      P=0.188N     P=0.174N   |  P<0.001N**   P=0.374      P=0.002N**   P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.071N     P=0.233      P=0.181N     P=0.187N   |  P<0.001N**   P=0.533      P=0.003N**   P<0.001N** |
|LOGISTIC REGRESSION    |  P=0.067N     P=0.267      P=0.176N     P=0.185N   |  P<0.001N**   P=0.476      P=0.003N**   P<0.001N** |
|COCHRAN-ARMITAGE       |  P=0.066N                                          |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.254      P=0.176N     P=0.184N   |               P=0.470      P=0.004N**   P<0.001N** |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  13
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/100 (4%)   4/50 (8%)    2/150 (1%)   1/100 (1%) | 28/100 (28%) 14/50 (28%)  19/150 (13%)  6/100 (6%) |
|ADJUSTED (b)           |   6.4%        10.9%         2.1%         1.9%      |  37.5%        41.2%        17.2%         8.0%      |
|TERMINAL (d)           |  2/50 (4%)    2/33 (6%)    1/71 (1%)    1/53 (2%)  | 16/60 (27%)   8/27 (30%)  13/99 (13%)   3/69 (4%)  |
|FIRST INCIDENCE (DAYS) |   617          654          597          732 (T)   |   586          630          595          630       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.071N     P=0.359      P=0.188N     P=0.174N   |  P<0.001N**   P=0.463      P=0.001N**   P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.071N     P=0.233      P=0.181N     P=0.187N   |  P<0.001N**   P=0.526N     P=0.002N**   P<0.001N** |
|LOGISTIC REGRESSION    |  P=0.067N     P=0.267      P=0.176N     P=0.185N   |  P<0.001N**   P=0.577      P=0.002N**   P<0.001N** |
|COCHRAN-ARMITAGE       |  P=0.066N                                          |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.254      P=0.176N     P=0.184N   |               P=0.580N     P=0.002N**   P<0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/100 (5%)   4/50 (8%)    2/150 (1%)   1/100 (1%) | 34/100 (34%) 14/50 (28%)  21/150 (14%)  6/100 (6%) |
|ADJUSTED (b)           |   8.3%        10.9%         2.1%         1.9%      |  43.4%        41.2%        19.0%         8.0%      |
|TERMINAL (d)           |  3/50 (6%)    2/33 (6%)    1/71 (1%)    1/53 (2%)  | 18/60 (30%)   8/27 (30%)  14/99 (14%)   3/69 (4%)  |
|FIRST INCIDENCE (DAYS) |   617          654          597          732 (T)   |   388          630          595          630       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.044N*    P=0.474      P=0.101N     P=0.100N   |  P<0.001N**   P=0.413N     P<0.001N**   P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.044N*    P=0.348      P=0.096N     P=0.107N   |  P<0.001N**   P=0.256N     P<0.001N**   P<0.001N** |
|LOGISTIC REGRESSION    |  P=0.042N*    P=0.373      P=0.092N     P=0.108N   |  P<0.001N**   P=0.282N     P<0.001N**   P<0.001N** |
|COCHRAN-ARMITAGE       |  P=0.040N*                                         |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.347      P=0.093N     P=0.106N   |               P=0.291N     P<0.001N**   P<0.001N** |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  14
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.5%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    1/71 (1%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          704          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.662N       (e)        P=0.329        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.671N       (e)        P=0.337        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.665N       (e)        P=0.334        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.664N                                          |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.359        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |  0/100 (0%)   0/50 (0%)    1/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.5%         0.0%      |   0.0%         0.0%         1.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    1/71 (1%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    1/99 (1%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          704          ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.662N       (e)        P=0.329        (e)      |  P=0.748N       (e)        P=0.600        (e)      |
|INCIDENTAL TUMOR       |  P=0.671N       (e)        P=0.337        (e)      |  P=0.748N       (e)        P=0.600        (e)      |
|LOGISTIC REGRESSION    |  P=0.665N       (e)        P=0.334        (e)      |  P=0.748N       (e)        P=0.600        (e)      |
|COCHRAN-ARMITAGE       |  P=0.664N                                          |  P=0.770N                                          |
|FISHER EXACT           |                 (e)        P=0.359        (e)      |                 (e)        P=0.600        (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  15
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 24/84 (29%)   6/20 (30%)  23/88 (26%)  19/97 (20%) | 51/91 (56%)  15/43 (35%)  47/100 (47%) 26/100 (26%)|
|ADJUSTED (b)           |  49.1%        76.9%        71.4%        28.6%      |  65.9%        56.3%        64.1%        33.4%      |
|TERMINAL (d)           | 14/34 (41%)   3/4 (75%)    8/12 (67%)  10/53 (19%) | 27/51 (53%)  10/20 (50%)  30/51 (59%)  19/69 (28%) |
|FIRST INCIDENCE (DAYS) |   519          617          518          568       |   470          425          470          575       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.027N*    P=0.506N     P=0.273      P=0.056N   |  P<0.001N**   P=0.087N     P=0.069N     P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.028N*    P=0.298      P=0.268      P=0.096N   |  P<0.001N**   P=0.023N*    P=0.146N     P<0.001N** |
|LOGISTIC REGRESSION    |  P=0.034N*    P=0.392      P=0.514      P=0.084N   |  P<0.001N**   P=0.016N*    P=0.144N     P<0.001N** |
|COCHRAN-ARMITAGE       |  P=0.076N                                          |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.549      P=0.426N     P=0.107N   |               P=0.017N*    P=0.135N     P<0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 24/84 (29%)   6/20 (30%)  23/88 (26%)  19/97 (20%) | 52/91 (57%)  15/43 (35%)  48/100 (48%) 26/100 (26%)|
|ADJUSTED (b)           |  49.1%        76.9%        71.4%        28.6%      |  67.3%        56.3%        64.4%        33.4%      |
|TERMINAL (d)           | 14/34 (41%)   3/4 (75%)    8/12 (67%)  10/53 (19%) | 28/51 (55%)  10/20 (50%)  30/51 (59%)  19/69 (28%) |
|FIRST INCIDENCE (DAYS) |   519          617          518          568       |   470          425          470          575       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.027N*    P=0.506N     P=0.273      P=0.056N   |  P<0.001N**   P=0.074N     P=0.067N     P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.028N*    P=0.298      P=0.268      P=0.096N   |  P<0.001N**   P=0.018N*    P=0.138N     P<0.001N** |
|LOGISTIC REGRESSION    |  P=0.034N*    P=0.392      P=0.514      P=0.084N   |  P<0.001N**   P=0.012N*    P=0.140N     P<0.001N** |
|COCHRAN-ARMITAGE       |  P=0.076N                                          |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.549      P=0.426N     P=0.107N   |               P=0.013N*    P=0.132N     P<0.001N** |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  16
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    2/150 (1%)   1/100 (1%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.6%         1.2%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    1/71 (1%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          709          639       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.397        (e)        P=0.324      P=0.500    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.384        (e)        P=0.337      P=0.485    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.394        (e)        P=0.334      P=0.518    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.397                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.359      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/100 (2%)   0/50 (0%)    5/150 (3%)   2/100 (2%) |  1/100 (1%)   0/50 (0%)    1/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   3.0%         0.0%         5.8%         3.6%      |   1.7%         0.0%         0.9%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    2/71 (3%)    1/53 (2%)  |  1/60 (2%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   666          ---          518          722       |   729 (T)      ---          699          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.555      P=0.365N     P=0.402      P=0.664N   |  P=0.391N     P=0.659N     P=0.648N     P=0.472N   |
|INCIDENTAL TUMOR       |  P=0.567      P=0.547N     P=0.407      P=0.659    |  P=0.464N     P=0.659N     P=0.690N     P=0.472N   |
|LOGISTIC REGRESSION    |  P=0.551      P=0.402N     P=0.408      P=0.692    |  P=0.413N     P=0.659N     P=0.660N     P=0.472N   |
|COCHRAN-ARMITAGE       |  P=0.555                                           |  P=0.419N                                          |
|FISHER EXACT           |               P=0.443N     P=0.418      P=0.689N   |               P=0.667N     P=0.641N     P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  17
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/100 (2%)   0/50 (0%)    1/150 (1%)   3/100 (3%) |  1/100 (1%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   3.3%         0.0%         1.4%         4.7%      |   1.4%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/50 (2%)    0/33 (0%)    1/71 (1%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   658          ---          732 (T)      666       |   677          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.235      P=0.363N     P=0.373N     P=0.526    |  P=0.438N     P=0.644N     P=0.414N     P=0.495N   |
|INCIDENTAL TUMOR       |  P=0.215      P=0.429N     P=0.363N     P=0.451    |  P=0.535N     P=0.648N     P=0.473N     P=0.629N   |
|LOGISTIC REGRESSION    |  P=0.227      P=0.397N     P=0.360N     P=0.497    |  P=0.442N     P=0.639N     P=0.421N     P=0.500N   |
|COCHRAN-ARMITAGE       |  P=0.231                                           |  P=0.443N                                          |
|FISHER EXACT           |               P=0.443N     P=0.351N     P=0.500    |               P=0.667N     P=0.400N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/100 (3%)   0/50 (0%)    3/150 (2%)   3/100 (3%) |  2/100 (2%)   0/50 (0%)    4/150 (3%)   1/100 (1%) |
|ADJUSTED (b)           |   5.3%         0.0%         4.2%         4.7%      |   3.0%         0.0%         4.0%         1.4%      |
|TERMINAL (d)           |  2/50 (4%)    0/33 (0%)    3/71 (4%)    0/53 (0%)  |  1/60 (2%)    0/27 (0%)    3/99 (3%)    1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   658          ---          732 (T)      666       |   677          ---          707          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.437      P=0.223N     P=0.488N     P=0.632N   |  P=0.427N     P=0.417N     P=0.572      P=0.465N   |
|INCIDENTAL TUMOR       |  P=0.423      P=0.262N     P=0.481N     P=0.625    |  P=0.503N     P=0.420N     P=0.519      P=0.541N   |
|LOGISTIC REGRESSION    |  P=0.431      P=0.253N     P=0.461N     P=0.659    |  P=0.461N     P=0.402N     P=0.553      P=0.494N   |
|COCHRAN-ARMITAGE       |  P=0.436                                           |  P=0.482N                                          |
|FISHER EXACT           |               P=0.293N     P=0.456N     P=0.659N   |               P=0.443N     P=0.544      P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  18
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |  1/100 (1%)   0/50 (0%)    4/150 (3%)   1/100 (1%) |
|ADJUSTED (b)           |   2.0%         0.0%         2.8%         0.0%      |   1.7%         0.0%         4.0%         1.4%      |
|TERMINAL (d)           |  1/50 (2%)    0/33 (0%)    2/71 (3%)    0/53 (0%)  |  1/60 (2%)    0/27 (0%)    3/99 (3%)    1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          732 (T)      ---       |   729 (T)      ---          707          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.405N     P=0.583N     P=0.621      P=0.488N   |  P=0.588N     P=0.659N     P=0.358      P=0.730N   |
|INCIDENTAL TUMOR       |  P=0.405N     P=0.583N     P=0.621      P=0.488N   |  P=0.633N     P=0.659N     P=0.330      P=0.730N   |
|LOGISTIC REGRESSION    |  P=0.405N     P=0.583N     P=0.621      P=0.488N   |  P=0.609N     P=0.659N     P=0.346      P=0.730N   |
|COCHRAN-ARMITAGE       |  P=0.402N                                          |  P=0.638                                           |
|FISHER EXACT           |               P=0.667N     P=0.649      P=0.500N   |               P=0.667N     P=0.335      P=0.751N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    2/150 (1%)   1/100 (1%) |  1/100 (1%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.6%         1.2%      |   1.7%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    1/71 (1%)    0/53 (0%)  |  1/60 (2%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          709          639       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.397        (e)        P=0.324      P=0.500    |  P=0.420N     P=0.659N     P=0.400N     P=0.472N   |
|INCIDENTAL TUMOR       |  P=0.384        (e)        P=0.337      P=0.485    |  P=0.420N     P=0.659N     P=0.400N     P=0.472N   |
|LOGISTIC REGRESSION    |  P=0.394        (e)        P=0.334      P=0.518    |  P=0.420N     P=0.659N     P=0.400N     P=0.472N   |
|COCHRAN-ARMITAGE       |  P=0.397                                           |  P=0.443N                                          |
|FISHER EXACT           |                 (e)        P=0.359      P=0.500    |               P=0.667N     P=0.400N     P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  19
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/100 (5%)   0/50 (0%)    9/150 (6%)   6/100 (6%) |  4/100 (4%)   0/50 (0%)    5/150 (3%)   1/100 (1%) |
|ADJUSTED (b)           |   8.2%         0.0%        11.3%         9.2%      |   6.3%         0.0%         4.9%         1.4%      |
|TERMINAL (d)           |  2/50 (4%)    0/33 (0%)    6/71 (8%)    1/53 (2%)  |  3/60 (5%)    0/27 (0%)    3/99 (3%)    1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   658          ---          518          639       |   677          ---          699          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.294      P=0.102N     P=0.456      P=0.540    |  P=0.184N     P=0.205N     P=0.479N     P=0.150N   |
|INCIDENTAL TUMOR       |  P=0.285      P=0.167N     P=0.465      P=0.441    |  P=0.249N     P=0.206N     P=0.545N     P=0.184N   |
|LOGISTIC REGRESSION    |  P=0.280      P=0.127N     P=0.477      P=0.431    |  P=0.210N     P=0.192N     P=0.503N     P=0.169N   |
|COCHRAN-ARMITAGE       |  P=0.289                                           |  P=0.229N                                          |
|FISHER EXACT           |               P=0.127N     P=0.485      P=0.500    |               P=0.194N     P=0.518N     P=0.184N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/100 (2%)   4/50 (8%)    3/150 (2%)   0/100 (0%) |  0/100 (0%)   0/50 (0%)    1/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   3.4%        11.3%         3.5%         0.0%      |   0.0%         0.0%         0.8%         0.0%      |
|TERMINAL (d)           |  1/50 (2%)    3/33 (9%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   666          654          664          ---       |   ---          ---          606          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.062N     P=0.155      P=0.670      P=0.229N   |  P=0.773N       (e)        P=0.583        (e)      |
|INCIDENTAL TUMOR       |  P=0.060N     P=0.093      P=0.653N     P=0.249N   |  P=0.800N       (e)        P=0.598        (e)      |
|LOGISTIC REGRESSION    |  P=0.060N     P=0.105      P=0.678N     P=0.240N   |  P=0.745N       (e)        P=0.555        (e)      |
|COCHRAN-ARMITAGE       |  P=0.059N                                          |  P=0.770N                                          |
|FISHER EXACT           |               P=0.096      P=0.665N     P=0.249N   |                 (e)        P=0.600        (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  20
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |  1/100 (1%)   0/50 (0%)    1/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   1.8%         0.0%         1.7%         0.0%      |   1.6%         0.0%         0.8%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   716          ---          568          ---       |   707          ---          659          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.403N     P=0.590N     P=0.640      P=0.489N   |  P=0.401N     P=0.658N     P=0.654N     P=0.477N   |
|INCIDENTAL TUMOR       |  P=0.415N     P=0.755N     P=0.660      P=0.530N   |  P=0.550N     P=0.648N     P=0.733N     P=0.629N   |
|LOGISTIC REGRESSION    |  P=0.392N     P=0.618N     P=0.648      P=0.496N   |  P=0.420N     P=0.641N     P=0.669N     P=0.498N   |
|COCHRAN-ARMITAGE       |  P=0.402N                                          |  P=0.419N                                          |
|FISHER EXACT           |               P=0.667N     P=0.649      P=0.500N   |               P=0.667N     P=0.641N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    2/150 (1%)   1/100 (1%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.0%         1.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          533          209       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.394        (e)        P=0.324      P=0.500    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.428        (e)        P=0.311        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.528        (e)        P=0.352        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.397                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.359      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  21
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/100 (3%)   4/50 (8%)    5/150 (3%)   0/100 (0%) |  1/100 (1%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   5.2%        11.3%         5.2%         0.0%      |   1.6%         0.0%         1.6%         0.0%      |
|TERMINAL (d)           |  1/50 (2%)    3/33 (9%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   666          654          568          ---       |   707          ---          606          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.044N*    P=0.263      P=0.582      P=0.115N   |  P=0.388N     P=0.658N     P=0.652      P=0.477N   |
|INCIDENTAL TUMOR       |  P=0.042N*    P=0.144      P=0.625      P=0.137N   |  P=0.522N     P=0.648N     P=0.587      P=0.629N   |
|LOGISTIC REGRESSION    |  P=0.042N*    P=0.192      P=0.587      P=0.122N   |  P=0.391N     P=0.641N     P=0.626      P=0.498N   |
|COCHRAN-ARMITAGE       |  P=0.040N*                                         |  P=0.402N                                          |
|FISHER EXACT           |               P=0.168      P=0.595      P=0.123N   |               P=0.667N     P=0.649      P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/100 (2%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   4.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  2/50 (4%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.208N     P=0.334N     P=0.166N     P=0.226N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.208N     P=0.334N     P=0.166N     P=0.226N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.208N     P=0.334N     P=0.166N     P=0.226N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.204N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.443N     P=0.159N     P=0.249N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  22
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 97/100 (97%) 47/50 (94%) 144/147 (98%) 91/98 (93%) |                                                    |
|ADJUSTED (b)           |  99.0%       100.0%       100.0%       100.0%      |                                                    |
|TERMINAL (d)           | 49/50 (98%)  33/33 (100%) 68/68 (100%) 53/53 (100%)|                                                    |
|FIRST INCIDENCE (DAYS) |   416          549          307          399       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.305N     P=0.030N*    P=0.404      P=0.173N   |                                                    |
|INCIDENTAL TUMOR       |  P=0.060N     P=0.595      P=0.368      P=0.141N   |                                                    |
|LOGISTIC REGRESSION    |  P=0.131N     P=0.475N     P=0.301      P=0.195N   |                                                    |
|COCHRAN-ARMITAGE       |  P=0.111N                                          |                                                    |
|FISHER EXACT           |               P=0.317N     P=0.466      P=0.157N   |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 22/75 (29%)   7/14 (50%)  17/72 (24%)  24/97 (25%) | 20/68 (29%)   5/19 (26%)   6/46 (13%)  10/99 (10%) |
|ADJUSTED (b)           |  33.8%       100.0%        15.2%        36.0%      |  40.7%         0.0%        52.0%        13.0%      |
|TERMINAL (d)           |  4/29 (14%)   1/1 (100%)   0/4 (0%)    13/53 (25%) | 10/31 (32%)   0/0          1/2 (50%)    5/69 (7%)  |
|FIRST INCIDENCE (DAYS) |   519          549          518          568       |   484          575          586          575       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.417N     P=0.285N     P=0.087N     P=0.351N   |  P<0.001N**   P=0.588      P=0.049N*    P=0.002N** |
|INCIDENTAL TUMOR       |  P=0.381N     P=0.227      P=0.064N     P=0.454N   |  P=0.003N**   P=0.587N     P=0.089N     P=0.006N** |
|LOGISTIC REGRESSION    |  P=0.190N     P=0.128      P=0.239N     P=0.295N   |  P<0.001N**   P=0.577N     P=0.072N     P=0.001N** |
|COCHRAN-ARMITAGE       |  P=0.205N                                          |  P=0.001N**                                        |
|FISHER EXACT           |               P=0.116      P=0.275N     P=0.307N   |               P=0.519N     P=0.033N*    P=0.001N** |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  23
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/75 (3%)    0/14 (0%)    3/72 (4%)    5/97 (5%)  |  2/68 (3%)    0/19 (0%)    0/46 (0%)    0/99 (0%)  |
|ADJUSTED (b)           |   6.9%         0.0%        50.5%         7.0%      |   2.7%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  2/29 (7%)    0/1 (0%)     2/4 (50%)    1/53 (2%)  |  0/31 (0%)    0/0          0/2 (0%)     0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          690          428       |   629          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.327      P=0.959N     P=0.038 *    P=0.339    |  P=0.197N     P=0.413N     P=0.150N     P=0.230N   |
|INCIDENTAL TUMOR       |  P=0.336      P=0.959N     P=0.037 *    P=0.300    |  P=0.245N     P=0.350N     P=0.184N     P=0.292N   |
|LOGISTIC REGRESSION    |  P=0.253      P=0.959N     P=0.153      P=0.327    |  P=0.142N     P=0.548N     P=0.339N     P=0.161N   |
|COCHRAN-ARMITAGE       |  P=0.243                                           |  P=0.143N                                          |
|FISHER EXACT           |               P=0.709N     P=0.481      P=0.340    |               P=0.609N     P=0.354N     P=0.164N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 24/75 (32%)   7/14 (50%)  20/72 (28%)  28/97 (29%) | 22/68 (32%)   5/19 (26%)   6/46 (13%)  10/99 (10%) |
|ADJUSTED (b)           |  39.1%       100.0%        58.1%        40.1%      |  42.3%         0.0%        52.0%        13.0%      |
|TERMINAL (d)           |  6/29 (21%)   1/1 (100%)   2/4 (50%)   14/53 (26%) | 10/31 (32%)   0/0          1/2 (50%)    5/69 (7%)  |
|FIRST INCIDENCE (DAYS) |   519          549          518          428       |   484          575          586          575       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.458N     P=0.276N     P=0.242N     P=0.421N   |  P<0.001N**   P=0.490N     P=0.016N*    P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.422N     P=0.242      P=0.228N     P=0.541N   |  P=0.001N**   P=0.401N     P=0.031N*    P=0.002N** |
|LOGISTIC REGRESSION    |  P=0.264N     P=0.166      P=0.355N     P=0.385N   |  P<0.001N**   P=0.474N     P=0.037N*    P<0.001N** |
|COCHRAN-ARMITAGE       |  P=0.287N                                          |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.160      P=0.353N     P=0.390N   |               P=0.420N     P=0.015N*    P<0.001N** |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  24
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/75 (4%)    0/14 (0%)    0/72 (0%)    1/97 (1%)  |  1/68 (1%)    0/19 (0%)    1/46 (2%)    1/99 (1%)  |
|ADJUSTED (b)           |   6.2%         0.0%         0.0%         1.8%      |   3.2%         0.0%         0.7%         1.4%      |
|TERMINAL (d)           |  1/29 (3%)    0/1 (0%)     0/4 (0%)     0/53 (0%)  |  1/31 (3%)    0/0          0/2 (0%)     1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   645          ---          ---          725       |   729 (T)      ---          536          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.284N     P=0.365N     P=0.137N     P=0.244N   |  P=0.454N       (e)        P=0.621      P=0.573N   |
|INCIDENTAL TUMOR       |  P=0.290N     P=0.523N     P=0.142N     P=0.291N   |  P=0.496N       (e)        P=0.571      P=0.573N   |
|LOGISTIC REGRESSION    |  P=0.222N     P=0.538N     P=0.145N     P=0.208N   |  P=0.582N       (e)        P=0.692      P=0.573N   |
|COCHRAN-ARMITAGE       |  P=0.253N                                          |  P=0.584N                                          |
|FISHER EXACT           |               P=0.595N     P=0.130N     P=0.221N   |               P=0.782N     P=0.646      P=0.650N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/75 (4%)    0/14 (0%)    0/72 (0%)    2/97 (2%)  |  1/68 (1%)    0/19 (0%)    1/46 (2%)    1/99 (1%)  |
|ADJUSTED (b)           |   6.2%         0.0%         0.0%         3.6%      |   3.2%         0.0%         0.7%         1.4%      |
|TERMINAL (d)           |  1/29 (3%)    0/1 (0%)     0/4 (0%)     1/53 (2%)  |  1/31 (3%)    0/0          0/2 (0%)     1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |   645          ---          ---          725       |   729 (T)      ---          536          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.463N     P=0.365N     P=0.137N     P=0.381N   |  P=0.454N       (e)        P=0.621      P=0.573N   |
|INCIDENTAL TUMOR       |  P=0.472N     P=0.523N     P=0.142N     P=0.433N   |  P=0.496N       (e)        P=0.571      P=0.573N   |
|LOGISTIC REGRESSION    |  P=0.413N     P=0.538N     P=0.145N     P=0.356N   |  P=0.582N       (e)        P=0.692      P=0.573N   |
|COCHRAN-ARMITAGE       |  P=0.484N                                          |  P=0.584N                                          |
|FISHER EXACT           |               P=0.595N     P=0.130N     P=0.380N   |               P=0.782N     P=0.646      P=0.650N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  25
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Tongue                                                                                                                           |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |  0/100 (0%)   0/50 (0%)    1/150 (1%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.5%         0.0%      |   0.0%         0.0%         1.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    1/71 (1%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    1/99 (1%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          704          ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.662N       (e)        P=0.329        (e)      |  P=0.748N       (e)        P=0.600        (e)      |
|INCIDENTAL TUMOR       |  P=0.671N       (e)        P=0.337        (e)      |  P=0.748N       (e)        P=0.600        (e)      |
|LOGISTIC REGRESSION    |  P=0.665N       (e)        P=0.334        (e)      |  P=0.748N       (e)        P=0.600        (e)      |
|COCHRAN-ARMITAGE       |  P=0.664N                                          |  P=0.770N                                          |
|FISHER EXACT           |                 (e)        P=0.359        (e)      |                 (e)        P=0.600        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Tongue                                                                                                                           |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    2/150 (1%)   0/100 (0%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.5%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    1/71 (1%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          704          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.662N       (e)        P=0.329        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.671N       (e)        P=0.337        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.665N       (e)        P=0.334        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.664N                                          |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.359        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  26
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/100 (0%)   0/50 (0%)    3/150 (2%)   1/100 (1%) |
|ADJUSTED (b)           |                                                    |   0.0%         0.0%         2.6%         1.4%      |
|TERMINAL (d)           |                                                    |  0/60 (0%)    0/27 (0%)    0/99 (0%)    1/69 (1%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          ---          630          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.462        (e)        P=0.212      P=0.528    |
|INCIDENTAL TUMOR       |                                                    |  P=0.342        (e)        P=0.169      P=0.528    |
|LOGISTIC REGRESSION    |                                                    |  P=0.440        (e)        P=0.195      P=0.528    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.438                                           |
|FISHER EXACT           |                                                    |                 (e)        P=0.214      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 11/100 (11%)  6/50 (12%)  35/150 (23%) 18/100 (18%)|
|ADJUSTED (b)           |                                                    |  15.3%        17.6%        31.0%        24.2%      |
|TERMINAL (d)           |                                                    |  6/60 (10%)   2/27 (7%)   24/99 (24%)  14/69 (20%) |
|FIRST INCIDENCE (DAYS) |                                                    |   388          593          512          622       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.294      P=0.481      P=0.025 *    P=0.184    |
|INCIDENTAL TUMOR       |                                                    |  P=0.120      P=0.544      P=0.010 **   P=0.111    |
|LOGISTIC REGRESSION    |                                                    |  P=0.158      P=0.531      P=0.012 *    P=0.112    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.164                                           |
|FISHER EXACT           |                                                    |               P=0.527      P=0.010 **   P=0.114    |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  27
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/100 (1%)   0/50 (0%)    3/150 (2%)   2/100 (2%) |
|ADJUSTED (b)           |                                                    |   1.4%         0.0%         2.6%         2.7%      |
|TERMINAL (d)           |                                                    |  0/60 (0%)    0/27 (0%)    1/99 (1%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   698          ---          509          672       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.389      P=0.659N     P=0.486      P=0.528    |
|INCIDENTAL TUMOR       |                                                    |  P=0.201      P=0.648N     P=0.391      P=0.278    |
|LOGISTIC REGRESSION    |                                                    |  P=0.361      P=0.639N     P=0.444      P=0.499    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.355                                           |
|FISHER EXACT           |                                                    |               P=0.667N     P=0.475      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 12/100 (12%)  6/50 (12%)  38/150 (25%) 20/100 (20%)|
|ADJUSTED (b)           |                                                    |  16.5%        17.6%        33.0%        26.2%      |
|TERMINAL (d)           |                                                    |  6/60 (10%)   2/27 (7%)   25/99 (25%)  14/69 (20%) |
|FIRST INCIDENCE (DAYS) |                                                    |   388          593          509          622       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.239      P=0.545      P=0.020 *    P=0.155    |
|INCIDENTAL TUMOR       |                                                    |  P=0.066      P=0.600N     P=0.006 **   P=0.060    |
|LOGISTIC REGRESSION    |                                                    |  P=0.114      P=0.601      P=0.008 **   P=0.086    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.120                                           |
|FISHER EXACT           |                                                    |               P=0.613N     P=0.007 **   P=0.088    |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  28
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    3/150 (2%)   1/100 (1%) |  1/100 (1%)   1/50 (2%)    1/150 (1%)   1/100 (1%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.3%         1.0%      |   1.2%         2.3%         0.8%         1.1%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          568          438       |   644          621          624          575       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.430        (e)        P=0.207      P=0.494    |  P=0.618N     P=0.589      P=0.669N     P=0.756    |
|INCIDENTAL TUMOR       |  P=0.461        (e)        P=0.198      P=0.527    |  P=0.678N     P=0.744      P=0.649N     P=0.766    |
|LOGISTIC REGRESSION    |  P=0.520        (e)        P=0.229      P=0.715    |  P=0.566N     P=0.582      P=0.689N     P=0.748N   |
|COCHRAN-ARMITAGE       |  P=0.438                                           |  P=0.613N                                          |
|FISHER EXACT           |                 (e)        P=0.214      P=0.500    |               P=0.557      P=0.641N     P=0.751N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    4/150 (3%)   1/100 (1%) |  1/100 (1%)   1/50 (2%)    1/150 (1%)   1/100 (1%) |
|ADJUSTED (b)           |   0.0%         0.0%         3.2%         1.0%      |   1.2%         2.3%         0.8%         1.1%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          568          438       |   644          621          624          575       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.464        (e)        P=0.134      P=0.494    |  P=0.618N     P=0.589      P=0.669N     P=0.756    |
|INCIDENTAL TUMOR       |  P=0.487        (e)        P=0.130      P=0.527    |  P=0.678N     P=0.744      P=0.649N     P=0.766    |
|LOGISTIC REGRESSION    |  P=0.543        (e)        P=0.144      P=0.715    |  P=0.566N     P=0.582      P=0.689N     P=0.748N   |
|COCHRAN-ARMITAGE       |  P=0.470                                           |  P=0.613N                                          |
|FISHER EXACT           |                 (e)        P=0.128      P=0.500    |               P=0.557      P=0.641N     P=0.751N   |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  29
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    3/150 (2%)   1/100 (1%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.9%         1.0%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          533          209       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.436        (e)        P=0.201      P=0.500    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.462        (e)        P=0.197        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.549        (e)        P=0.215        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.438                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.214      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/100 (0%)   0/50 (0%)    3/150 (2%)   1/100 (1%) |  0/100 (0%)   1/50 (2%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   0.0%         0.0%         2.9%         1.0%      |   0.0%         2.8%         0.0%         0.0%      |
|TERMINAL (d)           |  0/50 (0%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          533          209       |   ---          681          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.436        (e)        P=0.201      P=0.500    |  P=0.542N     P=0.359        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.462        (e)        P=0.197        (e)      |  P=0.649N     P=0.352        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.549        (e)        P=0.215        (e)      |  P=0.548N     P=0.361        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.438                                           |  P=0.548N                                          |
|FISHER EXACT           |                 (e)        P=0.214      P=0.500    |               P=0.333        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  30
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 50/100 (50%) 22/50 (44%)  55/150 (37%) 39/100 (39%)| 29/100 (29%) 21/50 (42%)  34/150 (23%) 21/100 (21%)|
|ADJUSTED (b)           |  58.6%        51.7%        49.4%        46.3%      |  36.8%        52.9%        26.9%        26.1%      |
|TERMINAL (d)           | 17/50 (34%)  13/33 (39%)  21/71 (30%)  12/53 (23%) | 13/60 (22%)  10/27 (37%)  13/99 (13%)  12/69 (17%) |
|FIRST INCIDENCE (DAYS) |   416          549          426          425       |   484          425          519          499       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.176N     P=0.120N     P=0.065N     P=0.102N   |  P=0.024N*    P=0.069      P=0.128N     P=0.085N   |
|INCIDENTAL TUMOR       |  P=0.119N     P=0.458      P=0.021N*    P=0.109N   |  P=0.131N     P=0.081      P=0.227N     P=0.284N   |
|LOGISTIC REGRESSION    |  P=0.148N     P=0.489N     P=0.033N*    P=0.132N   |  P=0.079N     P=0.080      P=0.154N     P=0.177N   |
|COCHRAN-ARMITAGE       |  P=0.116N                                          |  P=0.037N*                                         |
|FISHER EXACT           |               P=0.302N     P=0.025N*    P=0.077N   |               P=0.080      P=0.163N     P=0.126N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/100 (3%)   1/50 (2%)    7/150 (5%)   3/100 (3%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   5.0%         2.6%         6.4%         5.5%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/50 (2%)    0/33 (0%)    1/71 (1%)    2/53 (4%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   667          673          410          725       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.590      P=0.496N     P=0.375      P=0.628N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.575N     P=0.704N     P=0.355      P=0.640    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.576N     P=0.571N     P=0.405      P=0.657N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.593                                           |    (e)                                             |
|FISHER EXACT           |               P=0.593N     P=0.379      P=0.659N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  31
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   0/50 (0%)    2/150 (1%)   1/100 (1%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   2.0%         0.0%         1.8%         1.2%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/50 (2%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          652          609       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.609      P=0.583N     P=0.639      P=0.756N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.601      P=0.583N     P=0.654      P=0.759    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.622      P=0.583N     P=0.639      P=0.759N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.613                                           |    (e)                                             |
|FISHER EXACT           |               P=0.667N     P=0.649      P=0.751N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/100 (1%)   0/50 (0%)    2/150 (1%)   1/100 (1%) |  0/100 (0%)   0/50 (0%)    0/150 (0%)   0/100 (0%) |
|ADJUSTED (b)           |   2.0%         0.0%         1.8%         1.2%      |   0.0%         0.0%         0.0%         0.0%      |
|TERMINAL (d)           |  1/50 (2%)    0/33 (0%)    0/71 (0%)    0/53 (0%)  |  0/60 (0%)    0/27 (0%)    0/99 (0%)    0/69 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          652          609       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.609      P=0.583N     P=0.639      P=0.756N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.601      P=0.583N     P=0.654      P=0.759    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.622      P=0.583N     P=0.639      P=0.759N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.613                                           |    (e)                                             |
|FISHER EXACT           |               P=0.667N     P=0.649      P=0.751N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  32
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |100/100 (100% 48/50 (96%) 147/150 (98%) 97/100 (97%)| 74/100 (74%) 27/50 (54%)  94/150 (63%) 52/100 (52%)|
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  79.4%        64.5%        70.7%        62.3%      |
|TERMINAL (d)           | 50/50 (100%) 33/33 (100%) 71/71 (100%) 53/53 (100%)| 41/60 (68%)  13/27 (48%)  61/99 (62%)  38/69 (55%) |
|FIRST INCIDENCE (DAYS) |   416          549          307          399       |   388          425          439          575       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.475N     P=0.024N*    P=0.532      P=0.273N   |  P=0.002N**   P=0.117N     P=0.031N*    P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.268N       (e)        P=0.262N     P=0.262N   |  P=0.020N*    P=0.004N**   P=0.041N*    P=0.003N** |
|LOGISTIC REGRESSION    |  P=0.464N       (e)        P=0.443N     P=0.401N   |  P=0.014N*    P=0.003N**   P=0.026N*    P=0.002N** |
|COCHRAN-ARMITAGE       |  P=0.234N                                          |  P=0.005N**                                        |
|FISHER EXACT           |               P=0.110N     P=0.214N     P=0.123N   |               P=0.012N*    P=0.041N*    P=0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 66/100 (66%) 28/50 (56%)  82/150 (55%) 56/100 (56%)| 43/100 (43%) 23/50 (46%)  50/150 (33%) 30/100 (30%)|
|ADJUSTED (b)           |  71.4%        59.2%        63.0%        60.0%      |  50.7%        56.7%        37.3%        35.5%      |
|TERMINAL (d)           | 24/50 (48%)  14/33 (42%)  27/71 (38%)  17/53 (32%) | 19/60 (32%)  11/27 (41%)  18/99 (18%)  16/69 (23%) |
|FIRST INCIDENCE (DAYS) |   416          340          307          209       |   388          425          491          499       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.276N     P=0.060N     P=0.144N     P=0.141N   |  P=0.016N*    P=0.331      P=0.068N     P=0.028N*  |
|INCIDENTAL TUMOR       |  P=0.165N     P=0.435N     P=0.032N*    P=0.112N   |  P=0.134N     P=0.478      P=0.129N     P=0.155N   |
|LOGISTIC REGRESSION    |  P=0.182N     P=0.353N     P=0.058N     P=0.110N   |  P=0.064N     P=0.432      P=0.058N     P=0.065N   |
|COCHRAN-ARMITAGE       |  P=0.179N                                          |  P=0.023N*                                         |
|FISHER EXACT           |               P=0.155N     P=0.049N*    P=0.096N   |               P=0.430      P=0.079N     P=0.039N*  |
|=================================================================================================================================|
 
         DATE: 09/09/94                     EXPERIMENT: 05075 TEST: 01                                                 PAGE  33
                            STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DIPHENYLHYDANTOIN
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        240 PPM      800 PPM      2400 PPM  |   0 PPM        240 PPM      800 PPM      2400 PPM  |
|                       |   10-0         1-1          10-3         10-10     |   10-0         1-1          10-3         10-10     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |100/100 (100% 49/50 (98%) 149/150 (99%) 99/100 (99%)| 85/100 (85%) 40/50 (80%) 116/150 (77%) 65/100 (65%)|
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  87.6%        81.6%        79.4%        73.0%      |
|TERMINAL (d)           | 50/50 (100%) 33/33 (100%) 71/71 (100%) 53/53 (100%)| 48/60 (80%)  18/27 (67%)  69/99 (70%)  45/69 (65%) |
|FIRST INCIDENCE (DAYS) |   416          340          307          209       |   388          425          439          499       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.511      P=0.037N*    P=0.474      P=0.347N   |  P=0.001N**   P=0.522      P=0.076N     P=0.002N** |
|INCIDENTAL TUMOR       |  P=0.576N       (e)          (e)        P=0.527N   |  P=0.008N**   P=0.119N     P=0.099N     P=0.005N** |
|LOGISTIC REGRESSION    |  P=0.669        (e)          (e)        P=0.622N   |  P=0.004N**   P=0.111N     P=0.066N     P=0.002N** |
|COCHRAN-ARMITAGE       |  P=0.538N                                          |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.333N     P=0.600N     P=0.500N   |               P=0.290N     P=0.090N     P<0.001N** |
|=================================================================================================================================|
 
 (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).