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TDMS Study 05108-02 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                             PROMETHAZINE HYDROCHLORIDE                              DATE: 09/14/94       
EXPERIMENT: 05108 TEST: 02                                                                                     TIME: 00:32:03       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-45069          ROUTE: GAVAGE                                                                      NTP C#: C60673       
PATHOLOGIST: R. FLEISCHMAN                   K. MURTHY                                                         CAS: 58-33-3         
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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: Mason                                             PROMETHAZINE HYDROCHLORIDE                              DATE: 09/14/94      
EXPERIMENT: 05108 TEST: 02                                                                                     TIME: 00:32:03      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NO1-ES-45069          ROUTE: GAVAGE                                                                      NTP C#: C60673      
PATHOLOGIST: R. FLEISCHMAN                   K. MURTHY                                                         CAS: 58-33-3        
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                             PROMETHAZINE HYDROCHLORIDE                              DATE: 09/14/94       
EXPERIMENT: 05108 TEST: 02                                                                                     TIME: 00:32:03       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-45069          ROUTE: GAVAGE                                                                      NTP C#: C60673       
PATHOLOGIST: R. FLEISCHMAN                   K. MURTHY                                                         CAS: 58-33-3         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                   IN THE ANALYSIS OF THE STUDY OF PROMETHAZINE HYDROCHLORIDE
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             All Organs                    Malignant Tumors
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             All Organs                    Malignant Lymphoma And Histiocytic Sarcoma
 
              ====================================================================================================
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   1
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/58 (3%)    2/60 (3%)    5/58 (9%)    0/59 (0%)  |  2/60 (3%)    0/60 (0%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   4.9%         4.5%        12.4%         0.0%      |   5.1%         0.0%         2.6%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/37 (3%)    2/44 (5%)    4/39 (10%)   0/43 (0%)  |  2/39 (5%)    0/42 (0%)    1/39 (3%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   627          729 (T)      725          ---       |   736 (T)      ---          736 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.232N     P=0.644N     P=0.237      P=0.214N   |  P=0.184N     P=0.222N     P=0.500N     P=0.227N   |
|INCIDENTAL TUMOR       |  P=0.272N     P=0.683      P=0.104      P=0.294N   |  P=0.184N     P=0.222N     P=0.500N     P=0.227N   |
|LOGISTIC REGRESSION    |  P=0.234N     P=0.669N     P=0.221      P=0.228N   |  P=0.184N     P=0.222N     P=0.500N     P=0.227N   |
|COCHRAN-ARMITAGE       |  P=0.261N                                          |  P=0.188N                                          |
|FISHER EXACT           |               P=0.678N     P=0.219      P=0.244N   |               P=0.248N     P=0.500N     P=0.248N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/60 (3%)    2/60 (3%)    2/60 (3%)  |  2/60 (3%)    4/60 (7%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         4.4%         5.0%         4.4%      |   5.1%         9.0%         0.0%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    1/44 (2%)    2/40 (5%)    1/44 (2%)  |  2/39 (5%)    3/42 (7%)    0/39 (0%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          649          729 (T)      703       |   736 (T)      554          ---          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.271      P=0.261      P=0.244      P=0.269    |  P=0.194N     P=0.370      P=0.238N     P=0.483N   |
|INCIDENTAL TUMOR       |  P=0.281      P=0.177      P=0.244      P=0.253    |  P=0.182N     P=0.287      P=0.238N     P=0.483N   |
|LOGISTIC REGRESSION    |  P=0.263      P=0.241      P=0.244      P=0.256    |  P=0.205N     P=0.351      P=0.238N     P=0.483N   |
|COCHRAN-ARMITAGE       |  P=0.242                                           |  P=0.200N                                          |
|FISHER EXACT           |               P=0.248      P=0.248      P=0.248    |               P=0.340      P=0.248N     P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   2
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    2/60 (3%)    2/60 (3%)    2/60 (3%)  |  3/60 (5%)    4/60 (7%)    1/60 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |   2.5%         4.4%         5.0%         4.4%      |   7.4%         9.0%         2.3%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    1/44 (2%)    2/40 (5%)    1/44 (2%)  |  2/39 (5%)    3/42 (7%)    0/39 (0%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   722          649          729 (T)      703       |   720          554          707          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.458      P=0.533      P=0.509      P=0.541    |  P=0.136N     P=0.539      P=0.308N     P=0.289N   |
|INCIDENTAL TUMOR       |  P=0.475      P=0.348      P=0.506      P=0.515    |  P=0.147N     P=0.463      P=0.337N     P=0.328N   |
|LOGISTIC REGRESSION    |  P=0.449      P=0.509      P=0.508      P=0.531    |  P=0.142N     P=0.517      P=0.305N     P=0.304N   |
|COCHRAN-ARMITAGE       |  P=0.423                                           |  P=0.138N                                          |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.500    |               P=0.500      P=0.309N     P=0.309N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/60 (2%)    2/60 (3%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         2.3%         4.8%         2.3%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    1/44 (2%)    1/40 (3%)    1/44 (2%)  |  0/39 (0%)    0/42 (0%)    0/39 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      710          729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.392      P=0.524      P=0.248      P=0.524    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.401      P=0.524      P=0.243      P=0.524    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.391      P=0.524      P=0.240      P=0.524    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.367                                           |    (e)                                             |
|FISHER EXACT           |               P=0.500      P=0.248      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   3
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    2/60 (3%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         4.8%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/44 (0%)    1/40 (3%)    0/44 (0%)  |  0/39 (0%)    0/42 (0%)    0/39 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          710          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.611        (e)        P=0.248        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.619        (e)        P=0.243        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.610        (e)        P=0.240        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.595                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.248        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/60 (0%)    0/59 (0%)    3/60 (5%)  |  1/59 (2%)    0/59 (0%)    0/60 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   2.2%         0.0%         0.0%         6.8%      |   2.4%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/44 (0%)    0/40 (0%)    3/44 (7%)  |  0/38 (0%)    0/42 (0%)    0/39 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   627          ---          ---          729 (T)   |   718          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.099      P=0.496N     P=0.504N     P=0.347    |  P=0.306N     P=0.486N     P=0.500N     P=0.495N   |
|INCIDENTAL TUMOR       |  P=0.076      P=0.638N       (e)        P=0.277    |  P=0.354N     P=0.500N     P=0.536N     P=0.581N   |
|LOGISTIC REGRESSION    |  P=0.094      P=0.499N     P=0.505N     P=0.327    |  P=0.306N     P=0.490N     P=0.496N     P=0.500N   |
|COCHRAN-ARMITAGE       |  P=0.087                                           |  P=0.305N                                          |
|FISHER EXACT           |               P=0.500N     P=0.504N     P=0.309    |               P=0.500N     P=0.496N     P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   4
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/60 (3%)    0/59 (0%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         4.5%         0.0%         2.3%      |   0.0%         0.0%         2.1%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    2/44 (5%)    0/40 (0%)    1/44 (2%)  |  0/39 (0%)    0/42 (0%)    0/39 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          729 (T)   |   ---          ---          626          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.560      P=0.265        (e)        P=0.524    |  P=0.696        (e)        P=0.513        (e)      |
|INCIDENTAL TUMOR       |  P=0.560      P=0.265        (e)        P=0.524    |  P=0.738        (e)        P=0.602        (e)      |
|LOGISTIC REGRESSION    |  P=0.560      P=0.265        (e)        P=0.524    |  P=0.707        (e)        P=0.502        (e)      |
|COCHRAN-ARMITAGE       |  P=0.539                                           |  P=0.694                                           |
|FISHER EXACT           |               P=0.248        (e)        P=0.500    |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 17/60 (28%)  15/60 (25%)  15/59 (25%)  21/60 (35%) |  3/60 (5%)    4/60 (7%)    6/60 (10%)   9/60 (15%) |
|ADJUSTED (b)           |  36.5%        30.1%        33.9%        43.6%      |   7.7%         9.3%        14.7%        20.9%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   3/10 (30%)   1/10 (10%)   1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/9 (11%)  |
|TERMINAL (d)           | 10/39 (26%)  10/44 (23%)  12/40 (30%)  17/44 (39%) |  3/39 (8%)    3/42 (7%)    5/39 (13%)   8/41 (20%) |
|FIRST INCIDENCE (DAYS) |   458 (I)      458 (I)      444          460 (I)   |   736 (T)      725          629          462 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.284      P=0.319N     P=0.400N     P=0.433    |  P=0.031 *    P=0.542      P=0.246      P=0.071    |
|INCIDENTAL TUMOR       |  P=0.213      P=0.540N     P=0.563N     P=0.313    |  P=0.030 *    P=0.546      P=0.271      P=0.071    |
|LOGISTIC REGRESSION    |  P=0.226      P=0.523N     P=0.504N     P=0.283    |  P=0.025 *    P=0.540      P=0.243      P=0.060    |
|COCHRAN-ARMITAGE       |  P=0.190                                           |  P=0.029 *                                         |
|FISHER EXACT           |               P=0.418N     P=0.440N     P=0.278    |               P=0.500      P=0.245      P=0.063    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   5
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/60 (13%)   9/60 (15%)   5/59 (8%)    9/60 (15%) |  1/60 (2%)    1/60 (2%)    1/60 (2%)    2/60 (3%)  |
|ADJUSTED (b)           |  17.3%        18.9%        10.9%        19.4%      |   2.6%         2.4%         2.0%         4.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/39 (8%)    6/44 (14%)   2/40 (5%)    7/44 (16%) |  1/39 (3%)    1/42 (2%)    0/39 (0%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   362          460 (I)      522          631       |   736 (T)      736 (T)      569          734       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.523N     P=0.570      P=0.283N     P=0.589    |  P=0.357      P=0.745N     P=0.758N     P=0.520    |
|INCIDENTAL TUMOR       |  P=0.398      P=0.345      P=0.367N     P=0.347    |  P=0.345      P=0.745N     P=0.705N     P=0.465    |
|LOGISTIC REGRESSION    |  P=0.475      P=0.501      P=0.293N     P=0.522    |  P=0.343      P=0.745N     P=0.762N     P=0.510    |
|COCHRAN-ARMITAGE       |  P=0.511                                           |  P=0.351                                           |
|FISHER EXACT           |               P=0.500      P=0.290N     P=0.500    |               P=0.752N     P=0.752N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/60 (13%)   9/60 (15%)   5/59 (8%)   10/60 (17%) |  1/60 (2%)    1/60 (2%)    1/60 (2%)    2/60 (3%)  |
|ADJUSTED (b)           |  17.3%        18.9%        10.9%        21.6%      |   2.6%         2.4%         2.0%         4.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/39 (8%)    6/44 (14%)   2/40 (5%)    8/44 (18%) |  1/39 (3%)    1/42 (2%)    0/39 (0%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   362          460 (I)      522          631       |   736 (T)      736 (T)      569          734       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.468      P=0.570      P=0.283N     P=0.496    |  P=0.357      P=0.745N     P=0.758N     P=0.520    |
|INCIDENTAL TUMOR       |  P=0.290      P=0.345      P=0.367N     P=0.261    |  P=0.345      P=0.745N     P=0.705N     P=0.465    |
|LOGISTIC REGRESSION    |  P=0.365      P=0.501      P=0.293N     P=0.425    |  P=0.343      P=0.745N     P=0.762N     P=0.510    |
|COCHRAN-ARMITAGE       |  P=0.397                                           |  P=0.351                                           |
|FISHER EXACT           |               P=0.500      P=0.290N     P=0.399    |               P=0.752N     P=0.752N     P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   6
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 19/60 (32%)  22/60 (37%)  18/59 (31%)  26/60 (43%) |  4/60 (7%)    4/60 (7%)    7/60 (12%)  11/60 (18%) |
|ADJUSTED (b)           |  39.7%        43.6%        38.9%        52.9%      |  10.3%         9.3%        16.4%        25.1%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   4/10 (40%)   1/10 (10%)   1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/9 (11%)  |
|TERMINAL (d)           | 11/39 (28%)  16/44 (36%)  13/40 (33%)  21/44 (48%) |  4/39 (10%)   3/42 (7%)    5/39 (13%)   9/41 (22%) |
|FIRST INCIDENCE (DAYS) |   362          458 (I)      444          460 (I)   |   736 (T)      725          569          462 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.227      P=0.489      P=0.477N     P=0.267    |  P=0.016 *    P=0.600N     P=0.268      P=0.057    |
|INCIDENTAL TUMOR       |  P=0.119      P=0.276      P=0.562      P=0.099    |  P=0.014 *    P=0.596N     P=0.315      P=0.050 *  |
|LOGISTIC REGRESSION    |  P=0.156      P=0.355      P=0.522N     P=0.170    |  P=0.012 *    P=0.604N     P=0.262      P=0.045 *  |
|COCHRAN-ARMITAGE       |  P=0.130                                           |  P=0.015 *                                         |
|FISHER EXACT           |               P=0.350      P=0.525N     P=0.129    |               P=0.641N     P=0.264      P=0.048 *  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 19/60 (32%)  22/60 (37%)  18/59 (31%)  26/60 (43%) |  4/60 (7%)    4/60 (7%)    7/60 (12%)  11/60 (18%) |
|ADJUSTED (b)           |  39.7%        43.6%        38.9%        52.9%      |  10.3%         9.3%        16.4%        25.1%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   4/10 (40%)   1/10 (10%)   1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/9 (11%)  |
|TERMINAL (d)           | 11/39 (28%)  16/44 (36%)  13/40 (33%)  21/44 (48%) |  4/39 (10%)   3/42 (7%)    5/39 (13%)   9/41 (22%) |
|FIRST INCIDENCE (DAYS) |   362          458 (I)      444          460 (I)   |   736 (T)      725          569          462 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.227      P=0.489      P=0.477N     P=0.267    |  P=0.016 *    P=0.600N     P=0.268      P=0.057    |
|INCIDENTAL TUMOR       |  P=0.119      P=0.276      P=0.562      P=0.099    |  P=0.014 *    P=0.596N     P=0.315      P=0.050 *  |
|LOGISTIC REGRESSION    |  P=0.156      P=0.355      P=0.522N     P=0.170    |  P=0.012 *    P=0.604N     P=0.262      P=0.045 *  |
|COCHRAN-ARMITAGE       |  P=0.130                                           |  P=0.015 *                                         |
|FISHER EXACT           |               P=0.350      P=0.525N     P=0.129    |               P=0.641N     P=0.264      P=0.048 *  |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   7
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  9/60 (15%)   6/60 (10%)   6/60 (10%)   7/60 (12%) |  8/60 (13%)   2/60 (3%)    0/59 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |  22.2%        13.6%        14.5%        15.9%      |  17.7%         4.8%         0.0%         4.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  2/10 (20%)   0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/39 (21%)   6/44 (14%)   5/40 (13%)   7/44 (16%) |  4/39 (10%)   2/42 (5%)    0/38 (0%)    2/41 (5%)  |
|FIRST INCIDENCE (DAYS) |   580          729 (T)      693          729 (T)   |   464 (I)      736 (T)      ---          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.326N     P=0.213N     P=0.275N     P=0.299N   |  P=0.024N*    P=0.043N*    P=0.007N**   P=0.051N   |
|INCIDENTAL TUMOR       |  P=0.351N     P=0.240N     P=0.368N     P=0.333N   |  P=0.028N*    P=0.039N*    P=0.008N**   P=0.063N   |
|LOGISTIC REGRESSION    |  P=0.329N     P=0.250N     P=0.281N     P=0.318N   |  P=0.024N*    P=0.049N*    P=0.006N**   P=0.051N   |
|COCHRAN-ARMITAGE       |  P=0.393N                                          |  P=0.023N*                                         |
|FISHER EXACT           |               P=0.291N     P=0.291N     P=0.395N   |               P=0.047N*    P=0.003N**   P=0.047N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    6/60 (10%)   1/60 (2%)    1/60 (2%)  |  2/60 (3%)    0/60 (0%)    0/59 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   4.9%        12.9%         2.5%         2.3%      |   4.7%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/39 (3%)    5/44 (11%)   1/40 (3%)    1/44 (2%)  |  0/39 (0%)    0/42 (0%)    0/38 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   676          458 (I)      729 (T)      729 (T)   |   693          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.143N     P=0.173      P=0.491N     P=0.459N   |  P=0.117N     P=0.225N     P=0.239N     P=0.239N   |
|INCIDENTAL TUMOR       |  P=0.142N     P=0.139      P=0.494N     P=0.472N   |  P=0.146N     P=0.196N     P=0.270N     P=0.323N   |
|LOGISTIC REGRESSION    |  P=0.150N     P=0.140      P=0.498N     P=0.474N   |  P=0.117N     P=0.230N     P=0.242N     P=0.241N   |
|COCHRAN-ARMITAGE       |  P=0.163N                                          |  P=0.116N                                          |
|FISHER EXACT           |               P=0.136      P=0.500N     P=0.500N   |               P=0.248N     P=0.252N     P=0.248N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   8
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/60 (18%)  10/60 (17%)   7/60 (12%)   8/60 (13%) | 10/60 (17%)   2/60 (3%)    0/59 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |  26.5%        21.8%        17.0%        18.2%      |  21.5%         4.8%         0.0%         4.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  2/10 (20%)   0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  9/39 (23%)   9/44 (20%)   6/40 (15%)   8/44 (18%) |  4/39 (10%)   2/42 (5%)    0/38 (0%)    2/41 (5%)  |
|FIRST INCIDENCE (DAYS) |   580          458 (I)      693          729 (T)   |   464 (I)      736 (T)      ---          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.175N     P=0.394N     P=0.207N     P=0.216N   |  P=0.007N**   P=0.015N*    P=0.002N**   P=0.019N*  |
|INCIDENTAL TUMOR       |  P=0.189N     P=0.460N     P=0.279N     P=0.247N   |  P=0.009N**   P=0.010N*    P=0.002N**   P=0.024N*  |
|LOGISTIC REGRESSION    |  P=0.181N     P=0.468N     P=0.211N     P=0.234N   |  P=0.006N**   P=0.016N*    P=0.002N**   P=0.017N*  |
|COCHRAN-ARMITAGE       |  P=0.232N                                          |  P=0.006N**                                        |
|FISHER EXACT           |               P=0.500N     P=0.222N     P=0.309N   |               P=0.015N*    P<0.001N**   P=0.015N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/59 (0%)    2/59 (3%)    2/58 (3%)    1/58 (2%)  |
|ADJUSTED (b)           |                                                    |   0.0%         4.5%         5.4%         2.4%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  0/38 (0%)    1/41 (2%)    2/37 (5%)    0/40 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          693          736 (T)      734       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.473      P=0.255      P=0.232      P=0.515    |
|INCIDENTAL TUMOR       |                                                    |  P=0.412      P=0.265      P=0.232      P=0.419    |
|LOGISTIC REGRESSION    |                                                    |  P=0.459      P=0.247      P=0.232      P=0.502    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.463                                           |
|FISHER EXACT           |                                                    |               P=0.248      P=0.244      P=0.496    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE   9
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/58 (0%)    0/60 (0%)    0/55 (0%)    0/56 (0%)  |  5/56 (9%)    3/59 (5%)    4/59 (7%)    3/58 (5%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  13.4%         7.3%         9.3%         7.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/38 (0%)    0/44 (0%)    0/35 (0%)    0/40 (0%)  |  4/35 (11%)   3/41 (7%)    2/38 (5%)    3/39 (8%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   622          736 (T)      629          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.316N     P=0.280N     P=0.461N     P=0.306N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.279N     P=0.347N     P=0.359N     P=0.306N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.339N     P=0.293N     P=0.462N     P=0.335N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.329N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.329N     P=0.467N     P=0.339N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/58 (0%)    0/60 (0%)    0/55 (0%)    0/56 (0%)  |  5/56 (9%)    3/59 (5%)    5/59 (8%)    3/58 (5%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  13.4%         7.3%        11.3%         7.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/38 (0%)    0/44 (0%)    0/35 (0%)    0/40 (0%)  |  4/35 (11%)   3/41 (7%)    2/38 (5%)    3/39 (8%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   622          736 (T)      629          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.337N     P=0.280N     P=0.589N     P=0.306N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.287N     P=0.347N     P=0.465N     P=0.306N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.360N     P=0.293N     P=0.593N     P=0.335N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.349N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.329N     P=0.595N     P=0.339N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  10
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  2/60 (3%)    2/60 (3%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.6%         4.6%         0.0%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/44 (0%)    0/40 (0%)    0/44 (0%)  |  1/39 (3%)    1/42 (2%)    0/39 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   582          722          ---          734       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.293N     P=0.666N     P=0.240N     P=0.491N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.324N     P=0.632      P=0.185N     P=0.541N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.302N     P=0.689N     P=0.238N     P=0.504N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.296N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.691N     P=0.248N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  2/60 (3%)    2/60 (3%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.6%         4.6%         0.0%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/44 (0%)    0/40 (0%)    0/44 (0%)  |  1/39 (3%)    1/42 (2%)    0/39 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   582          722          ---          734       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.293N     P=0.666N     P=0.240N     P=0.491N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.324N     P=0.632      P=0.185N     P=0.541N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.302N     P=0.689N     P=0.238N     P=0.504N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.296N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.691N     P=0.248N     P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  11
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    2/60 (3%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   2.6%         4.6%         0.0%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/44 (0%)    0/40 (0%)    0/44 (0%)  |  1/39 (3%)    1/42 (2%)    0/39 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   736 (T)      722          ---          734       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.490N     P=0.531      P=0.500N     P=0.747N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.566N     P=0.535      P=0.500N     P=0.722    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.506N     P=0.523      P=0.500N     P=0.759N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.500N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.500      P=0.500N     P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    1/58 (2%)    0/60 (0%)    2/60 (3%)  |  0/59 (0%)    0/59 (0%)    0/59 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         2.4%         0.0%         4.3%      |   0.0%         0.0%         0.0%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/38 (0%)    1/42 (2%)    0/40 (0%)    1/44 (2%)  |  0/38 (0%)    0/42 (0%)    0/38 (0%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          669       |   ---          ---          ---          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.161      P=0.520        (e)        P=0.268    |  P=0.204        (e)          (e)        P=0.515    |
|INCIDENTAL TUMOR       |  P=0.168      P=0.520        (e)        P=0.256    |  P=0.204        (e)          (e)        P=0.515    |
|LOGISTIC REGRESSION    |  P=0.156      P=0.520        (e)        P=0.254    |  P=0.204        (e)          (e)        P=0.515    |
|COCHRAN-ARMITAGE       |  P=0.144                                           |  P=0.201                                           |
|FISHER EXACT           |               P=0.496        (e)        P=0.252    |                 (e)          (e)        P=0.504    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  12
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    1/60 (2%)    1/60 (2%)    2/60 (3%)  |
|ADJUSTED (b)           |   2.6%         0.0%         0.0%         0.0%      |   2.6%         2.4%         2.6%         4.9%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/39 (3%)    0/44 (0%)    0/40 (0%)    0/44 (0%)  |  1/39 (3%)    1/42 (2%)    1/39 (3%)    2/41 (5%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          ---          ---       |   736 (T)      736 (T)      736 (T)      736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.296N     P=0.476N     P=0.495N     P=0.476N   |  P=0.359      P=0.745N     P=0.762      P=0.517    |
|INCIDENTAL TUMOR       |  P=0.296N     P=0.476N     P=0.495N     P=0.476N   |  P=0.359      P=0.745N     P=0.762      P=0.517    |
|LOGISTIC REGRESSION    |  P=0.296N     P=0.476N     P=0.495N     P=0.476N   |  P=0.359      P=0.745N     P=0.762      P=0.517    |
|COCHRAN-ARMITAGE       |  P=0.306N                                          |  P=0.351                                           |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.500N   |               P=0.752N     P=0.752N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/58 (0%)    1/60 (2%)    0/58 (0%)    0/60 (0%)  |  4/60 (7%)    2/60 (3%)    1/57 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         2.3%         0.0%         0.0%      |   9.6%         4.8%         2.7%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/37 (0%)    1/44 (2%)    0/38 (0%)    0/44 (0%)  |  3/39 (8%)    2/42 (5%)    1/37 (3%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   582          736 (T)      736 (T)      736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.549N     P=0.535        (e)          (e)      |  P=0.111N     P=0.309N     P=0.194N     P=0.172N   |
|INCIDENTAL TUMOR       |  P=0.549N     P=0.535        (e)          (e)      |  P=0.103N     P=0.385N     P=0.177N     P=0.170N   |
|LOGISTIC REGRESSION    |  P=0.549N     P=0.535        (e)          (e)      |  P=0.118N     P=0.322N     P=0.197N     P=0.184N   |
|COCHRAN-ARMITAGE       |  P=0.564N                                          |  P=0.115N                                          |
|FISHER EXACT           |               P=0.508        (e)          (e)      |               P=0.340N     P=0.198N     P=0.182N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  13
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/58 (0%)    1/60 (2%)    1/58 (2%)    0/60 (0%)  |  4/60 (7%)    2/60 (3%)    1/57 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         2.3%         2.4%         0.0%      |   9.6%         4.8%         2.7%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/37 (0%)    1/44 (2%)    0/38 (0%)    0/44 (0%)  |  3/39 (8%)    2/42 (5%)    1/37 (3%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      725          ---       |   582          736 (T)      736 (T)      736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.573N     P=0.535      P=0.510        (e)      |  P=0.111N     P=0.309N     P=0.194N     P=0.172N   |
|INCIDENTAL TUMOR       |  P=0.560N     P=0.535      P=0.500        (e)      |  P=0.103N     P=0.385N     P=0.177N     P=0.170N   |
|LOGISTIC REGRESSION    |  P=0.569N     P=0.535      P=0.504        (e)      |  P=0.118N     P=0.322N     P=0.197N     P=0.184N   |
|COCHRAN-ARMITAGE       |  P=0.590N                                          |  P=0.115N                                          |
|FISHER EXACT           |               P=0.508      P=0.500        (e)      |               P=0.340N     P=0.198N     P=0.182N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/60 (2%)    3/60 (5%)    3/60 (5%)    2/60 (3%)  |
|ADJUSTED (b)           |                                                    |   2.6%         6.9%         6.9%         3.5%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    1/9 (11%)    2/9 (22%)  |
|TERMINAL (d)           |                                                    |  1/39 (3%)    2/42 (5%)    2/39 (5%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   736 (T)      725          464 (I)      462 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.466      P=0.335      P=0.297      P=0.481    |
|INCIDENTAL TUMOR       |                                                    |  P=0.442      P=0.341      P=0.297      P=0.481    |
|LOGISTIC REGRESSION    |                                                    |  P=0.500      P=0.330      P=0.306      P=0.569    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.477                                           |
|FISHER EXACT           |                                                    |               P=0.309      P=0.309      P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  14
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/60 (2%)    1/60 (2%)    2/60 (3%)  |  0/60 (0%)    1/60 (2%)    2/60 (3%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         2.3%         2.3%         4.5%      |   0.0%         2.4%         4.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    1/44 (2%)    0/40 (0%)    2/44 (5%)  |  0/39 (0%)    1/42 (2%)    1/39 (3%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      666          729 (T)   |   ---          736 (T)      701          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.172      P=0.524      P=0.505      P=0.265    |  P=0.615N     P=0.515      P=0.240        (e)      |
|INCIDENTAL TUMOR       |  P=0.179      P=0.524      P=0.500      P=0.265    |  P=0.651N     P=0.515      P=0.220        (e)      |
|LOGISTIC REGRESSION    |  P=0.167      P=0.524      P=0.500      P=0.265    |  P=0.623N     P=0.515      P=0.238        (e)      |
|COCHRAN-ARMITAGE       |  P=0.153                                           |  P=0.616N                                          |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.248    |               P=0.500      P=0.248        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    3/60 (5%)    0/60 (0%)    3/60 (5%)  |  0/60 (0%)    0/60 (0%)    1/60 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         6.8%         0.0%         6.5%      |   0.0%         0.0%         2.1%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    3/44 (7%)    0/40 (0%)    2/44 (5%)  |  0/39 (0%)    0/42 (0%)    0/39 (0%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          669       |   ---          ---          626          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.187      P=0.143        (e)        P=0.145    |  P=0.237        (e)        P=0.513      P=0.510    |
|INCIDENTAL TUMOR       |  P=0.192      P=0.143        (e)        P=0.138    |  P=0.262        (e)        P=0.602      P=0.510    |
|LOGISTIC REGRESSION    |  P=0.183      P=0.143        (e)        P=0.133    |  P=0.233        (e)        P=0.502      P=0.510    |
|COCHRAN-ARMITAGE       |  P=0.164                                           |  P=0.236                                           |
|FISHER EXACT           |               P=0.122        (e)        P=0.122    |                 (e)        P=0.500      P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  15
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    3/60 (5%)    1/60 (2%)    4/60 (7%)  |  0/60 (0%)    1/60 (2%)    3/60 (5%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         6.8%         2.3%         8.8%      |   0.0%         2.4%         6.8%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    3/44 (7%)    0/40 (0%)    3/44 (7%)  |  0/39 (0%)    1/42 (2%)    1/39 (3%)    1/41 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      666          669       |   ---          736 (T)      626          736 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.089      P=0.143      P=0.505      P=0.081    |  P=0.354      P=0.515      P=0.128      P=0.510    |
|INCIDENTAL TUMOR       |  P=0.093      P=0.143      P=0.500      P=0.077    |  P=0.345      P=0.515      P=0.141      P=0.510    |
|LOGISTIC REGRESSION    |  P=0.084      P=0.143      P=0.500      P=0.073    |  P=0.343      P=0.515      P=0.121      P=0.510    |
|COCHRAN-ARMITAGE       |  P=0.072                                           |  P=0.351                                           |
|FISHER EXACT           |               P=0.122      P=0.500      P=0.059    |               P=0.500      P=0.122      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/60 (0%)    1/60 (2%)    0/60 (0%)  |  0/60 (0%)    2/60 (3%)    1/60 (2%)    2/60 (3%)  |
|ADJUSTED (b)           |   2.4%         0.0%         2.4%         0.0%      |   0.0%         4.3%         2.3%         4.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/44 (0%)    0/40 (0%)    0/44 (0%)  |  0/39 (0%)    0/42 (0%)    0/39 (0%)    0/41 (0%)  |
|FIRST INCIDENCE (DAYS) |   698          ---          725          ---       |   ---          677          701          643       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.388N     P=0.481N     P=0.752N     P=0.477N   |  P=0.242      P=0.260      P=0.500      P=0.242    |
|INCIDENTAL TUMOR       |  P=0.367N     P=0.638N     P=0.777      P=0.500N   |  P=0.146      P=0.265      P=0.464      P=0.196    |
|LOGISTIC REGRESSION    |  P=0.393N     P=0.495N     P=0.761N     P=0.490N   |  P=0.306      P=0.244      P=0.500      P=0.241    |
|COCHRAN-ARMITAGE       |  P=0.405N                                          |  P=0.246                                           |
|FISHER EXACT           |               P=0.500N     P=0.752N     P=0.500N   |               P=0.248      P=0.500      P=0.248    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  16
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    8/60 (13%)   7/60 (12%)   4/60 (7%)  |  8/60 (13%)  18/60 (30%)  15/60 (25%)  12/60 (20%) |
|ADJUSTED (b)           |   9.9%        16.5%        16.2%         8.5%      |  19.9%        38.1%        35.4%        27.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/39 (8%)    6/44 (14%)   4/40 (10%)   2/44 (5%)  |  7/39 (18%)  13/42 (31%)  12/39 (31%)   9/41 (22%) |
|FIRST INCIDENCE (DAYS) |   698          128          666          568       |   718          677          626          643       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.373N     P=0.234      P=0.285      P=0.577N   |  P=0.426      P=0.041 *    P=0.083      P=0.265    |
|INCIDENTAL TUMOR       |  P=0.532N     P=0.192      P=0.259      P=0.640    |  P=0.336      P=0.036 *    P=0.077      P=0.213    |
|LOGISTIC REGRESSION    |  P=0.474N     P=0.180      P=0.265      P=0.611N   |  P=0.335      P=0.030 *    P=0.075      P=0.220    |
|COCHRAN-ARMITAGE       |  P=0.426N                                          |  P=0.406                                           |
|FISHER EXACT           |               P=0.181      P=0.264      P=0.641N   |               P=0.022 *    P=0.082      P=0.232    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    8/60 (13%)   6/60 (10%)   4/60 (7%)  |  8/60 (13%)  16/60 (27%)  14/60 (23%)  10/60 (17%) |
|ADJUSTED (b)           |   7.7%        16.5%        14.1%         8.5%      |  19.9%        35.3%        33.9%        23.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/39 (8%)    6/44 (14%)   4/40 (10%)   2/44 (5%)  |  7/39 (18%)  13/42 (31%)  12/39 (31%)   9/41 (22%) |
|FIRST INCIDENCE (DAYS) |   729 (T)      128          666          568       |   718          693          626          679       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.461N     P=0.138      P=0.259      P=0.562    |  P=0.522N     P=0.081      P=0.118      P=0.438    |
|INCIDENTAL TUMOR       |  P=0.485      P=0.130      P=0.252      P=0.495    |  P=0.511      P=0.082      P=0.118      P=0.397    |
|LOGISTIC REGRESSION    |  P=0.553      P=0.103      P=0.246      P=0.532    |  P=0.516      P=0.070      P=0.112      P=0.396    |
|COCHRAN-ARMITAGE       |  P=0.515N                                          |  P=0.543N                                          |
|FISHER EXACT           |               P=0.102      P=0.245      P=0.500    |               P=0.054      P=0.119      P=0.399    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  17
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 26/60 (43%)  25/60 (42%)  24/60 (40%)  30/60 (50%) | 26/60 (43%)  20/60 (33%)  17/60 (28%)  18/60 (30%) |
|ADJUSTED (b)           |  55.0%        49.7%        50.5%        62.4%      |  54.6%        44.2%        38.8%        39.1%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   3/10 (30%)   1/10 (10%)   1/10 (10%) |  2/10 (20%)   0/10 (0%)    1/9 (11%)    3/9 (33%)  |
|TERMINAL (d)           | 18/39 (46%)  19/44 (43%)  17/40 (43%)  26/44 (59%) | 18/39 (46%)  17/42 (40%)  13/39 (33%)  14/41 (34%) |
|FIRST INCIDENCE (DAYS) |   458 (I)      458 (I)      444          460 (I)   |   442          554          464 (I)      462 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.379      P=0.335N     P=0.402N     P=0.509    |  P=0.087N     P=0.120N     P=0.077N     P=0.085N   |
|INCIDENTAL TUMOR       |  P=0.291      P=0.570      P=0.533N     P=0.370    |  P=0.092N     P=0.206N     P=0.053N     P=0.115N   |
|LOGISTIC REGRESSION    |  P=0.271      P=0.556      P=0.493N     P=0.345    |  P=0.100N     P=0.140N     P=0.062N     P=0.101N   |
|COCHRAN-ARMITAGE       |  P=0.234                                           |  P=0.087N                                          |
|FISHER EXACT           |               P=0.500N     P=0.427N     P=0.292    |               P=0.174N     P=0.064N     P=0.092N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 15/60 (25%)  23/60 (38%)  14/60 (23%)  19/60 (32%) | 16/60 (27%)  21/60 (35%)  19/60 (32%)  17/60 (28%) |
|ADJUSTED (b)           |  31.2%        44.4%        29.7%        38.6%      |  34.7%        43.6%        40.9%        36.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    2/10 (20%)   0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  7/39 (18%)  16/44 (36%)   7/40 (18%)  14/44 (32%) |  9/39 (23%)  15/42 (36%)  12/39 (31%)  12/41 (29%) |
|FIRST INCIDENCE (DAYS) |   283          128          522          568       |   582          677          569          561       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.526N     P=0.169      P=0.479N     P=0.414    |  P=0.493N     P=0.314      P=0.359      P=0.542    |
|INCIDENTAL TUMOR       |  P=0.241      P=0.030 *    P=0.536      P=0.118    |  P=0.461      P=0.268      P=0.361      P=0.383    |
|LOGISTIC REGRESSION    |  P=0.446      P=0.084      P=0.499N     P=0.301    |  P=0.456      P=0.196      P=0.390      P=0.381    |
|COCHRAN-ARMITAGE       |  P=0.434                                           |  P=0.509N                                          |
|FISHER EXACT           |               P=0.085      P=0.500N     P=0.272    |               P=0.215      P=0.344      P=0.500    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 02                                                 PAGE  18
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      11.25        22.5         45.0      |   VEHICLE      3.75         7.5          15.0      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/60 (53%)  40/60 (67%)  30/60 (50%)  38/60 (63%) | 34/60 (57%)  33/60 (55%)  30/60 (50%)  29/60 (48%) |
|ADJUSTED (b)           |  63.6%        72.5%        59.8%        74.5%      |  67.8%        66.0%        62.1%        58.7%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   5/10 (50%)   1/10 (10%)   1/10 (10%) |  2/10 (20%)   0/10 (0%)    1/9 (11%)    3/9 (33%)  |
|TERMINAL (d)           | 21/39 (54%)  29/44 (66%)  20/40 (50%)  31/44 (70%) | 23/39 (59%)  25/42 (60%)  21/39 (54%)  21/41 (51%) |
|FIRST INCIDENCE (DAYS) |   283          128          444          460 (I)   |   442          554          464 (I)      462 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.495      P=0.280      P=0.403N     P=0.424    |  P=0.193N     P=0.354N     P=0.321N     P=0.215N   |
|INCIDENTAL TUMOR       |  P=0.189      P=0.053      P=0.576N     P=0.103    |  P=0.219N     P=0.477N     P=0.229N     P=0.303N   |
|LOGISTIC REGRESSION    |  P=0.361      P=0.097      P=0.419N     P=0.255    |  P=0.192N     P=0.479N     P=0.282N     P=0.258N   |
|COCHRAN-ARMITAGE       |  P=0.298                                           |  P=0.179N                                          |
|FISHER EXACT           |               P=0.096      P=0.428N     P=0.177    |               P=0.500N     P=0.292N     P=0.232N   |
|=================================================================================================================================|
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   458
          Female interim sacrifices(days): 462
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
 
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.