National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/1901

TDMS Study 05108-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                             PROMETHAZINE HYDROCHLORIDE                              DATE: 09/13/94       
EXPERIMENT: 05108 TEST: 01                                                                                     TIME: 21:49:52       
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         
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               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: 09/13/94      
EXPERIMENT: 05108 TEST: 01                                                                                     TIME: 21:49:52      
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        
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                             PROMETHAZINE HYDROCHLORIDE                              DATE: 09/13/94       
EXPERIMENT: 05108 TEST: 01                                                                                     TIME: 21:49:52       
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 RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Mammary Gland                 Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                             Skin                          Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma
                             Testes                        Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Mammary Gland                 Adenoma
                                                           Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                             Uterus                        Polyp Stromal
                                                           Sarcoma Stromal or Polyp Stromal
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   1
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/60 (23%)  11/60 (18%)   9/59 (15%)   2/59 (3%)  |  4/60 (7%)    1/59 (2%)    2/60 (3%)    3/58 (5%)  |
|ADJUSTED (b)           |  42.3%        43.5%        33.2%         7.9%      |  12.5%         2.6%         5.7%        12.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  6/23 (26%)   5/18 (28%)   0/11 (0%)    0/10 (0%)  |  4/32 (13%)   0/34 (0%)    1/31 (3%)    3/24 (13%) |
|FIRST INCIDENCE (DAYS) |   570          568          462 (I)      565       |   729 (T)      676          643          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.065N     P=0.578      P=0.582      P=0.050N   |  P=0.487      P=0.162N     P=0.348N     P=0.657    |
|INCIDENTAL TUMOR       |  P=0.002N**   P=0.510N     P=0.192N     P=0.002N** |  P=0.533      P=0.177N     P=0.298N     P=0.657    |
|LOGISTIC REGRESSION    |  P=0.006N**   P=0.542N     P=0.306N     P=0.007N** |  P=0.496      P=0.159N     P=0.347N     P=0.657    |
|COCHRAN-ARMITAGE       |  P=0.001N**                                        |  P=0.558N                                          |
|FISHER EXACT           |               P=0.327N     P=0.189N     P=0.001N** |               P=0.187N     P=0.340N     P=0.519N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    1/60 (2%)    1/59 (2%)    1/59 (2%)  |  0/60 (0%)    0/59 (0%)    0/60 (0%)    0/58 (0%)  |
|ADJUSTED (b)           |   8.4%         5.6%         5.0%         4.8%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  0/23 (0%)    1/18 (6%)    0/11 (0%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   570          717 (T)      691          657       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.448N     P=0.416N     P=0.432N     P=0.541N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.263N     P=0.361N     P=0.243N     P=0.295N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.323N     P=0.354N     P=0.352N     P=0.370N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.248N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.309N     P=0.316N     P=0.316N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   2
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/60 (27%)  12/60 (20%)  10/59 (17%)   4/59 (7%)  |  4/60 (7%)    1/59 (2%)    2/60 (3%)    3/58 (5%)  |
|ADJUSTED (b)           |  46.0%        47.9%        36.5%        15.2%      |  12.5%         2.6%         5.7%        12.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  6/23 (26%)   6/18 (33%)   0/11 (0%)    0/10 (0%)  |  4/32 (13%)   0/34 (0%)    1/31 (3%)    3/24 (13%) |
|FIRST INCIDENCE (DAYS) |   570          568          462 (I)      565       |   729 (T)      676          643          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.134N     P=0.544N     P=0.553N     P=0.124N   |  P=0.487      P=0.162N     P=0.348N     P=0.657    |
|INCIDENTAL TUMOR       |  P=0.004N**   P=0.450N     P=0.130N     P=0.005N** |  P=0.533      P=0.177N     P=0.298N     P=0.657    |
|LOGISTIC REGRESSION    |  P=0.005N**   P=0.482N     P=0.262N     P=0.017N*  |  P=0.496      P=0.159N     P=0.347N     P=0.657    |
|COCHRAN-ARMITAGE       |  P=0.003N**                                        |  P=0.558N                                          |
|FISHER EXACT           |               P=0.259N     P=0.144N     P=0.003N** |               P=0.187N     P=0.340N     P=0.519N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/58 (3%)    5/60 (8%)    2/58 (3%)    3/59 (5%)  |  3/56 (5%)    9/55 (16%)   1/58 (2%)    2/57 (4%)  |
|ADJUSTED (b)           |   8.3%        16.6%        11.8%        22.1%      |  10.7%        24.6%         3.1%         6.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    1/18 (6%)    1/11 (9%)    2/10 (20%) |  3/28 (11%)   5/30 (17%)   0/29 (0%)    1/24 (4%)  |
|FIRST INCIDENCE (DAYS) |   716          491          616          583       |   729 (T)      597          689          550       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.280      P=0.146      P=0.467      P=0.206    |  P=0.201N     P=0.085      P=0.302N     P=0.563N   |
|INCIDENTAL TUMOR       |  P=0.454      P=0.327      P=0.618      P=0.334    |  P=0.132N     P=0.099      P=0.297N     P=0.477N   |
|LOGISTIC REGRESSION    |  P=0.485      P=0.204      P=0.594      P=0.298    |  P=0.164N     P=0.077      P=0.294N     P=0.554N   |
|COCHRAN-ARMITAGE       |  P=0.577N                                          |  P=0.121N                                          |
|FISHER EXACT           |               P=0.234      P=0.691N     P=0.508    |               P=0.058      P=0.296N     P=0.492N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   3
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/58 (3%)    5/60 (8%)    2/58 (3%)    3/59 (5%)  |  3/56 (5%)    9/55 (16%)   1/58 (2%)    3/57 (5%)  |
|ADJUSTED (b)           |   8.3%        16.6%        11.8%        22.1%      |  10.7%        24.6%         3.1%        10.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    1/18 (6%)    1/11 (9%)    2/10 (20%) |  3/28 (11%)   5/30 (17%)   0/29 (0%)    2/24 (8%)  |
|FIRST INCIDENCE (DAYS) |   716          491          616          583       |   729 (T)      597          689          550       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.280      P=0.146      P=0.467      P=0.206    |  P=0.349N     P=0.085      P=0.302N     P=0.597    |
|INCIDENTAL TUMOR       |  P=0.454      P=0.327      P=0.618      P=0.334    |  P=0.256N     P=0.099      P=0.297N     P=0.660N   |
|LOGISTIC REGRESSION    |  P=0.485      P=0.204      P=0.594      P=0.298    |  P=0.302N     P=0.077      P=0.294N     P=0.605    |
|COCHRAN-ARMITAGE       |  P=0.577N                                          |  P=0.229N                                          |
|FISHER EXACT           |               P=0.234      P=0.691N     P=0.508    |               P=0.058      P=0.296N     P=0.652N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/60 (8%)    2/60 (3%)    2/59 (3%)    1/58 (2%)  |  2/60 (3%)    1/59 (2%)    0/60 (0%)    0/55 (0%)  |
|ADJUSTED (b)           |  17.0%        11.1%         8.5%         4.5%      |   6.3%         2.9%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  3/23 (13%)   2/18 (11%)   0/11 (0%)    0/10 (0%)  |  2/32 (6%)    1/34 (3%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   462 (I)      717 (T)      666          656       |   729 (T)      729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.273N     P=0.321N     P=0.462N     P=0.321N   |  P=0.126N     P=0.479N     P=0.245N     P=0.303N   |
|INCIDENTAL TUMOR       |  P=0.187N     P=0.307N     P=0.326N     P=0.251N   |  P=0.126N     P=0.479N     P=0.245N     P=0.303N   |
|LOGISTIC REGRESSION    |  P=0.139N     P=0.288N     P=0.276N     P=0.162N   |  P=0.126N     P=0.479N     P=0.245N     P=0.303N   |
|COCHRAN-ARMITAGE       |  P=0.084N                                          |  P=0.108N                                          |
|FISHER EXACT           |               P=0.219N     P=0.226N     P=0.111N   |               P=0.506N     P=0.248N     P=0.270N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   4
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    0/59 (0%)    0/57 (0%)  |
|ADJUSTED (b)           |   8.7%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  2/23 (9%)    0/18 (0%)    0/11 (0%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.209N     P=0.293N     P=0.411N     P=0.434N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.209N     P=0.293N     P=0.411N     P=0.434N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.209N     P=0.293N     P=0.411N     P=0.434N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.116N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/60 (2%)    1/60 (2%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    0/59 (0%)    0/57 (0%)  |
|ADJUSTED (b)           |   8.7%         4.5%         9.1%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  2/23 (9%)    0/18 (0%)    1/11 (9%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      696          717 (T)      ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.328N     P=0.580N     P=0.725      P=0.434N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.287N     P=0.582N     P=0.725      P=0.434N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.298N     P=0.596N     P=0.725      P=0.434N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.153N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   5
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    2/60 (3%)    2/60 (3%)    1/60 (2%)  |  0/60 (0%)    0/59 (0%)    1/60 (2%)    1/59 (2%)  |
|ADJUSTED (b)           |  16.0%         9.8%        11.6%         5.9%      |   0.0%         0.0%         3.2%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  3/23 (13%)   1/18 (6%)    1/11 (9%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    1/31 (3%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   687          696          598          667       |   ---          ---          729 (T)      640       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.389N     P=0.454N     P=0.619N     P=0.487N   |  P=0.181        (e)        P=0.494      P=0.446    |
|INCIDENTAL TUMOR       |  P=0.259N     P=0.451N     P=0.526N     P=0.387N   |  P=0.257        (e)        P=0.494      P=0.682    |
|LOGISTIC REGRESSION    |  P=0.273N     P=0.467N     P=0.481N     P=0.390N   |  P=0.196        (e)        P=0.494      P=0.480    |
|COCHRAN-ARMITAGE       |  P=0.138N                                          |  P=0.234                                           |
|FISHER EXACT           |               P=0.340N     P=0.340N     P=0.182N   |                 (e)        P=0.500      P=0.496    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    2/60 (3%)    3/60 (5%)    1/60 (2%)  |  0/60 (0%)    0/59 (0%)    1/60 (2%)    1/59 (2%)  |
|ADJUSTED (b)           |  16.0%         9.8%        13.5%         5.9%      |   0.0%         0.0%         3.2%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  3/23 (13%)   1/18 (6%)    1/11 (9%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    1/31 (3%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   687          696          479          667       |   ---          ---          729 (T)      640       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.422N     P=0.454N     P=0.549      P=0.487N   |  P=0.181        (e)        P=0.494      P=0.446    |
|INCIDENTAL TUMOR       |  P=0.286N     P=0.451N     P=0.573N     P=0.387N   |  P=0.257        (e)        P=0.494      P=0.682    |
|LOGISTIC REGRESSION    |  P=0.256N     P=0.467N     P=0.575N     P=0.390N   |  P=0.196        (e)        P=0.494      P=0.480    |
|COCHRAN-ARMITAGE       |  P=0.163N                                          |  P=0.234                                           |
|FISHER EXACT           |               P=0.340N     P=0.500N     P=0.182N   |                 (e)        P=0.500      P=0.496    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   6
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    2/60 (3%)    3/60 (5%)    1/60 (2%)  |  0/60 (0%)    0/59 (0%)    1/60 (2%)    1/59 (2%)  |
|ADJUSTED (b)           |  16.0%         9.8%        13.5%         5.9%      |   0.0%         0.0%         3.2%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  3/23 (13%)   1/18 (6%)    1/11 (9%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    1/31 (3%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   687          696          479          667       |   ---          ---          729 (T)      640       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.422N     P=0.454N     P=0.549      P=0.487N   |  P=0.181        (e)        P=0.494      P=0.446    |
|INCIDENTAL TUMOR       |  P=0.286N     P=0.451N     P=0.573N     P=0.387N   |  P=0.257        (e)        P=0.494      P=0.682    |
|LOGISTIC REGRESSION    |  P=0.256N     P=0.467N     P=0.575N     P=0.390N   |  P=0.196        (e)        P=0.494      P=0.480    |
|COCHRAN-ARMITAGE       |  P=0.163N                                          |  P=0.234                                           |
|FISHER EXACT           |               P=0.340N     P=0.500N     P=0.182N   |                 (e)        P=0.500      P=0.496    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/60 (0%)    0/59 (0%)    1/60 (2%)  |  2/60 (3%)    1/59 (2%)    0/60 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   4.3%         0.0%         0.0%         1.9%      |   5.1%         2.9%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    0/18 (0%)    0/11 (0%)    0/10 (0%)  |  1/32 (3%)    1/34 (3%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      ---          ---          462 (I)   |   451 (I)      729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.496      P=0.549N     P=0.647N     P=0.658    |  P=0.128N     P=0.486N     P=0.243N     P=0.313N   |
|INCIDENTAL TUMOR       |  P=0.496      P=0.549N     P=0.647N     P=0.658    |  P=0.128N     P=0.486N     P=0.243N     P=0.313N   |
|LOGISTIC REGRESSION    |  P=0.603      P=0.549N     P=0.647N     P=0.759N   |  P=0.103N     P=0.510N     P=0.242N     P=0.233N   |
|COCHRAN-ARMITAGE       |  P=0.594                                           |  P=0.102N                                          |
|FISHER EXACT           |               P=0.500N     P=0.504N     P=0.752N   |               P=0.506N     P=0.248N     P=0.252N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   7
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   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)            |  1/60 (2%)    0/60 (0%)    1/59 (2%)    1/60 (2%)  |  2/60 (3%)    1/59 (2%)    1/60 (2%)    0/59 (0%)  |
|ADJUSTED (b)           |   4.3%         0.0%         9.1%         1.9%      |   5.1%         2.9%         3.2%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    0/18 (0%)    1/11 (9%)    0/10 (0%)  |  1/32 (3%)    1/34 (3%)    1/31 (3%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      ---          717 (T)      462 (I)   |   451 (I)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.383      P=0.549N     P=0.589      P=0.658    |  P=0.201N     P=0.486N     P=0.507N     P=0.313N   |
|INCIDENTAL TUMOR       |  P=0.383      P=0.549N     P=0.589      P=0.658    |  P=0.201N     P=0.486N     P=0.507N     P=0.313N   |
|LOGISTIC REGRESSION    |  P=0.511      P=0.549N     P=0.589      P=0.759N   |  P=0.169N     P=0.510N     P=0.500N     P=0.233N   |
|COCHRAN-ARMITAGE       |  P=0.539                                           |  P=0.155N                                          |
|FISHER EXACT           |               P=0.500N     P=0.748      P=0.752N   |               P=0.506N     P=0.500N     P=0.252N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    1/60 (2%)    0/60 (0%)    1/60 (2%)  |  3/60 (5%)    3/60 (5%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   4.3%         5.6%         0.0%        10.0%      |   8.4%         8.5%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    1/18 (6%)    0/11 (0%)    1/10 (10%) |  2/32 (6%)    2/34 (6%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      717 (T)      ---          717 (T)   |   513          704          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.478      P=0.707      P=0.647N     P=0.566    |  P=0.052N     P=0.629N     P=0.125N     P=0.168N   |
|INCIDENTAL TUMOR       |  P=0.478      P=0.707      P=0.647N     P=0.566    |  P=0.048N*    P=0.549      P=0.175N     P=0.149N   |
|LOGISTIC REGRESSION    |  P=0.478      P=0.707      P=0.647N     P=0.566    |  P=0.045N*    P=0.634N     P=0.120N     P=0.143N   |
|COCHRAN-ARMITAGE       |  P=0.617N                                          |  P=0.035N*                                         |
|FISHER EXACT           |               P=0.752N     P=0.500N     P=0.752N   |               P=0.660N     P=0.122N     P=0.122N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   8
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    2/60 (3%)    0/60 (0%)    0/60 (0%)  | 14/60 (23%)  13/60 (22%)  10/60 (17%)   6/60 (10%) |
|ADJUSTED (b)           |  16.0%        11.1%         0.0%         0.0%      |  42.0%        36.1%        29.0%        19.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  3/23 (13%)   2/18 (11%)   0/11 (0%)    0/10 (0%)  | 13/32 (41%)  11/34 (32%)   7/31 (23%)   3/24 (13%) |
|FIRST INCIDENCE (DAYS) |   687          717 (T)      ---          ---       |   547          692          652          421       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.072N     P=0.457N     P=0.171N     P=0.212N   |  P=0.101N     P=0.421N     P=0.260N     P=0.133N   |
|INCIDENTAL TUMOR       |  P=0.061N     P=0.452N     P=0.141N     P=0.176N   |  P=0.075N     P=0.409N     P=0.234N     P=0.079N   |
|LOGISTIC REGRESSION    |  P=0.059N     P=0.466N     P=0.134N     P=0.181N   |  P=0.080N     P=0.415N     P=0.251N     P=0.104N   |
|COCHRAN-ARMITAGE       |  P=0.018N*                                         |  P=0.025N*                                         |
|FISHER EXACT           |               P=0.340N     P=0.059N     P=0.059N   |               P=0.500N     P=0.247N     P=0.042N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/60 (8%)    3/60 (5%)    0/60 (0%)    1/60 (2%)  | 15/60 (25%)  15/60 (25%)  10/60 (17%)   6/60 (10%) |
|ADJUSTED (b)           |  20.2%        16.7%         0.0%        10.0%      |  43.4%        40.5%        29.0%        19.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  4/23 (17%)   3/18 (17%)   0/11 (0%)    1/10 (10%) | 13/32 (41%)  12/34 (35%)   7/31 (23%)   3/24 (13%) |
|FIRST INCIDENCE (DAYS) |   687          717 (T)      ---          717 (T)   |   513          692          652          421       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.175N     P=0.499N     P=0.119N     P=0.380N   |  P=0.059N     P=0.502N     P=0.195N     P=0.095N   |
|INCIDENTAL TUMOR       |  P=0.156N     P=0.495N     P=0.097N     P=0.336N   |  P=0.038N*    P=0.575N     P=0.197N     P=0.050N   |
|LOGISTIC REGRESSION    |  P=0.149N     P=0.509N     P=0.088N     P=0.345N   |  P=0.041N*    P=0.488N     P=0.181N     P=0.066N   |
|COCHRAN-ARMITAGE       |  P=0.038N*                                         |  P=0.012N*                                         |
|FISHER EXACT           |               P=0.359N     P=0.029N*    P=0.103N   |               P=0.583N     P=0.184N     P=0.026N*  |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE   9
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/60 (8%)    3/60 (5%)    0/60 (0%)    1/60 (2%)  | 15/60 (25%)  15/60 (25%)  10/60 (17%)   6/60 (10%) |
|ADJUSTED (b)           |  20.2%        16.7%         0.0%        10.0%      |  43.4%        40.5%        29.0%        19.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  4/23 (17%)   3/18 (17%)   0/11 (0%)    1/10 (10%) | 13/32 (41%)  12/34 (35%)   7/31 (23%)   3/24 (13%) |
|FIRST INCIDENCE (DAYS) |   687          717 (T)      ---          717 (T)   |   513          692          652          421       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.175N     P=0.499N     P=0.119N     P=0.380N   |  P=0.059N     P=0.502N     P=0.195N     P=0.095N   |
|INCIDENTAL TUMOR       |  P=0.156N     P=0.495N     P=0.097N     P=0.336N   |  P=0.038N*    P=0.575N     P=0.197N     P=0.050N   |
|LOGISTIC REGRESSION    |  P=0.149N     P=0.509N     P=0.088N     P=0.345N   |  P=0.041N*    P=0.488N     P=0.181N     P=0.066N   |
|COCHRAN-ARMITAGE       |  P=0.038N*                                         |  P=0.012N*                                         |
|FISHER EXACT           |               P=0.359N     P=0.029N*    P=0.103N   |               P=0.583N     P=0.184N     P=0.026N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    2/60 (3%)    1/59 (2%)    0/60 (0%)  |  0/60 (0%)    0/59 (0%)    0/60 (0%)    0/56 (0%)  |
|ADJUSTED (b)           |   7.9%        10.5%         7.7%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    1/18 (6%)    0/11 (0%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   697          716          704          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.307N     P=0.603      P=0.696N     P=0.433N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.200N     P=0.608      P=0.554N     P=0.357N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.269N     P=0.596      P=0.652N     P=0.395N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.127N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.691N     P=0.506N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  10
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   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)            | 21/60 (35%)  18/60 (30%)  17/58 (29%)   8/59 (14%) | 28/59 (47%)  26/58 (45%)  23/58 (40%)  18/58 (31%) |
|ADJUSTED (b)           |  49.7%        57.3%        56.8%        48.6%      |  70.8%        60.7%        55.4%        54.0%      |
|INTERIM SACRIFICE 1 (c)|  5/10 (50%)   2/10 (20%)   1/10 (10%)   0/9 (0%)   |  2/10 (20%)   2/10 (20%)   1/10 (10%)   1/7 (14%)  |
|TERMINAL (d)           |  5/23 (22%)   7/18 (39%)   2/11 (18%)   4/10 (40%) | 20/31 (65%)  18/34 (53%)  13/31 (42%)  10/24 (42%) |
|FIRST INCIDENCE (DAYS) |   462 (I)      462 (I)      401          565       |   450 (I)      451 (I)      451 (I)      442       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.238N     P=0.486      P=0.356      P=0.226N   |  P=0.271N     P=0.277N     P=0.245N     P=0.282N   |
|INCIDENTAL TUMOR       |  P=0.011N*    P=0.505N     P=0.256N     P=0.023N*  |  P=0.060N     P=0.155N     P=0.128N     P=0.076N   |
|LOGISTIC REGRESSION    |  P=0.012N*    P=0.424N     P=0.360N     P=0.014N*  |  P=0.087N     P=0.303N     P=0.167N     P=0.124N   |
|COCHRAN-ARMITAGE       |  P=0.005N**                                        |  P=0.032N*                                         |
|FISHER EXACT           |               P=0.348N     P=0.322N     P=0.006N** |               P=0.460N     P=0.253N     P=0.051N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|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%        16.1%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  0/23 (0%)    0/18 (0%)    1/11 (9%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          704          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.432        (e)        P=0.109        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.496        (e)        P=0.173        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.449        (e)        P=0.133        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.597                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.248        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  11
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |  13.0%         5.6%         0.0%         0.0%      |   0.0%         2.1%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  3/23 (13%)   1/18 (6%)    0/11 (0%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      717 (T)      ---          ---       |   ---          597          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.121N     P=0.394N     P=0.275N     P=0.298N   |  P=0.622N     P=0.532        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.121N     P=0.394N     P=0.275N     P=0.298N   |  P=0.483N     P=0.682        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.121N     P=0.394N     P=0.275N     P=0.298N   |  P=0.557N     P=0.482        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.044N*                                         |  P=0.568N                                          |
|FISHER EXACT           |               P=0.309N     P=0.122N     P=0.122N   |               P=0.500        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   8.7%         5.6%         0.0%         0.0%      |   0.0%         2.1%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  2/23 (9%)    1/18 (6%)    0/11 (0%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      717 (T)      ---          ---       |   ---          597          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.214N     P=0.586N     P=0.411N     P=0.434N   |  P=0.622N     P=0.532        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.214N     P=0.586N     P=0.411N     P=0.434N   |  P=0.483N     P=0.682        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.214N     P=0.586N     P=0.411N     P=0.434N   |  P=0.557N     P=0.482        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.101N                                          |  P=0.568N                                          |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |               P=0.500        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  12
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/60 (7%)    1/60 (2%)    2/60 (3%)    0/60 (0%)  |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |  14.5%         5.6%        16.1%         0.0%      |   0.0%         5.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  3/23 (13%)   1/18 (6%)    1/11 (9%)    0/10 (0%)  |  0/32 (0%)    1/34 (3%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   462 (I)      717 (T)      704          ---       |   ---          597          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.166N     P=0.241N     P=0.623N     P=0.168N   |  P=0.467N     P=0.264        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.146N     P=0.241N     P=0.561N     P=0.168N   |  P=0.373N     P=0.344        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.092N     P=0.222N     P=0.423N     P=0.086N   |  P=0.431N     P=0.245        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.053N                                          |  P=0.405N                                          |
|FISHER EXACT           |               P=0.182N     P=0.340N     P=0.059N   |               P=0.248        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    3/60 (5%)    4/60 (7%)    2/60 (3%)  |  1/60 (2%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   8.5%         7.7%        12.4%         9.0%      |   3.1%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  0/23 (0%)    0/18 (0%)    0/11 (0%)    0/10 (0%)  |  1/32 (3%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   595          529          520          617       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.540      P=0.543      P=0.348      P=0.601    |  P=0.339N     P=0.488N     P=0.506N     P=0.557N   |
|INCIDENTAL TUMOR       |  P=0.275N     P=0.564N     P=0.603N     P=0.429N   |  P=0.339N     P=0.488N     P=0.506N     P=0.557N   |
|LOGISTIC REGRESSION    |  P=0.202N     P=0.591N     P=0.487      P=0.587N   |  P=0.339N     P=0.488N     P=0.506N     P=0.557N   |
|COCHRAN-ARMITAGE       |  P=0.420N                                          |  P=0.307N                                          |
|FISHER EXACT           |               P=0.660N     P=0.500      P=0.500N   |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  13
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   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)            |  3/60 (5%)    3/60 (5%)    5/60 (8%)    2/60 (3%)  |  1/60 (2%)    0/60 (0%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   8.5%         7.7%        14.4%         9.0%      |   3.1%         0.0%         0.0%         3.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  0/23 (0%)    0/18 (0%)    0/11 (0%)    0/10 (0%)  |  1/32 (3%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   595          529          520          617       |   729 (T)      ---          ---          629       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.517      P=0.543      P=0.229      P=0.601    |  P=0.535      P=0.488N     P=0.506N     P=0.695    |
|INCIDENTAL TUMOR       |  P=0.270N     P=0.564N     P=0.586      P=0.429N   |  P=0.627      P=0.488N     P=0.506N     P=0.703N   |
|LOGISTIC REGRESSION    |  P=0.204N     P=0.591N     P=0.534      P=0.587N   |  P=0.559      P=0.488N     P=0.506N     P=0.723    |
|COCHRAN-ARMITAGE       |  P=0.442N                                          |  P=0.595                                           |
|FISHER EXACT           |               P=0.660N     P=0.359      P=0.500N   |               P=0.500N     P=0.500N     P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 52/60 (87%)  48/60 (80%)  50/60 (83%)  50/60 (83%) |                                                    |
|ADJUSTED (b)           | 100.0%        97.9%       100.0%        98.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  5/10 (50%)   4/10 (40%)   6/10 (60%)   7/9 (78%)  |                                                    |
|TERMINAL (d)           | 23/23 (100%) 17/18 (94%)  11/11 (100%)  9/10 (90%) |                                                    |
|FIRST INCIDENCE (DAYS) |   462 (I)      462 (I)      462 (I)      458       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.200      P=0.009 **   P<0.001 ** |                                                    |
|INCIDENTAL TUMOR       |  P=0.139      P=0.446N     P=0.525      P=0.260    |                                                    |
|LOGISTIC REGRESSION    |  P=0.143      P=0.599N     P=0.589      P=0.243    |                                                    |
|COCHRAN-ARMITAGE       |  P=0.454N                                          |                                                    |
|FISHER EXACT           |               P=0.232N     P=0.399N     P=0.399N   |                                                    |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  14
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/59 (7%)    5/59 (8%)    3/54 (6%)    2/50 (4%)  |  4/59 (7%)    4/59 (7%)   10/55 (18%)   2/54 (4%)  |
|ADJUSTED (b)           |  11.6%        21.0%        15.6%        11.7%      |  12.5%        11.3%        32.3%         8.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    2/18 (11%)   1/11 (9%)    1/10 (10%) |  4/32 (13%)   3/34 (9%)   10/31 (32%)   2/24 (8%)  |
|FIRST INCIDENCE (DAYS) |   602          563          625          462 (I)   |   729 (T)      692          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.503N     P=0.346      P=0.580      P=0.590N   |  P=0.551      P=0.608N     P=0.058      P=0.475N   |
|INCIDENTAL TUMOR       |  P=0.315N     P=0.423      P=0.561N     P=0.431N   |  P=0.557      P=0.614N     P=0.058      P=0.475N   |
|LOGISTIC REGRESSION    |  P=0.358N     P=0.414      P=0.626N     P=0.450N   |  P=0.539      P=0.606N     P=0.057      P=0.475N   |
|COCHRAN-ARMITAGE       |  P=0.275N                                          |  P=0.440N                                          |
|FISHER EXACT           |               P=0.500      P=0.550N     P=0.421N   |               P=0.642N     P=0.058      P=0.383N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/59 (7%)    5/59 (8%)    3/54 (6%)    2/50 (4%)  |  4/59 (7%)    4/59 (7%)   10/55 (18%)   3/54 (6%)  |
|ADJUSTED (b)           |  11.6%        21.0%        15.6%        11.7%      |  12.5%        11.3%        32.3%        12.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    2/18 (11%)   1/11 (9%)    1/10 (10%) |  4/32 (13%)   3/34 (9%)   10/31 (32%)   3/24 (13%) |
|FIRST INCIDENCE (DAYS) |   602          563          625          462 (I)   |   729 (T)      692          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.503N     P=0.346      P=0.580      P=0.590N   |  P=0.389      P=0.608N     P=0.058      P=0.657    |
|INCIDENTAL TUMOR       |  P=0.315N     P=0.423      P=0.561N     P=0.431N   |  P=0.394      P=0.614N     P=0.058      P=0.657    |
|LOGISTIC REGRESSION    |  P=0.358N     P=0.414      P=0.626N     P=0.450N   |  P=0.375      P=0.606N     P=0.057      P=0.657    |
|COCHRAN-ARMITAGE       |  P=0.275N                                          |  P=0.540                                           |
|FISHER EXACT           |               P=0.500      P=0.550N     P=0.421N   |               P=0.642N     P=0.058      P=0.550N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  15
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    1/59 (2%)    1/54 (2%)    0/50 (0%)  |  2/59 (3%)    2/59 (3%)    2/55 (4%)    0/54 (0%)  |
|ADJUSTED (b)           |   4.3%         2.1%         5.0%         0.0%      |   6.3%         5.9%         6.5%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    0/18 (0%)    0/11 (0%)    0/10 (0%)  |  2/32 (6%)    2/34 (6%)    2/31 (6%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      491          691          ---       |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.441N     P=0.729      P=0.638      P=0.666N   |  P=0.226N     P=0.674N     P=0.684      P=0.303N   |
|INCIDENTAL TUMOR       |  P=0.455N     P=0.631N     P=0.673      P=0.666N   |  P=0.226N     P=0.674N     P=0.684      P=0.303N   |
|LOGISTIC REGRESSION    |  P=0.370N     P=0.753N     P=0.652      P=0.666N   |  P=0.226N     P=0.674N     P=0.684      P=0.303N   |
|COCHRAN-ARMITAGE       |  P=0.351N                                          |  P=0.185N                                          |
|FISHER EXACT           |               P=0.752N     P=0.730      P=0.541N   |               P=0.691N     P=0.664      P=0.270N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    1/59 (2%)    1/54 (2%)    0/50 (0%)  |  2/59 (3%)    2/59 (3%)    3/55 (5%)    0/54 (0%)  |
|ADJUSTED (b)           |   4.3%         2.1%         5.0%         0.0%      |   6.3%         5.9%         9.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  1/23 (4%)    0/18 (0%)    0/11 (0%)    0/10 (0%)  |  2/32 (6%)    2/34 (6%)    3/31 (10%)   0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   717 (T)      491          691          ---       |   729 (T)      729 (T)      729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.441N     P=0.729      P=0.638      P=0.666N   |  P=0.279N     P=0.674N     P=0.485      P=0.303N   |
|INCIDENTAL TUMOR       |  P=0.455N     P=0.631N     P=0.673      P=0.666N   |  P=0.279N     P=0.674N     P=0.485      P=0.303N   |
|LOGISTIC REGRESSION    |  P=0.370N     P=0.753N     P=0.652      P=0.666N   |  P=0.279N     P=0.674N     P=0.485      P=0.303N   |
|COCHRAN-ARMITAGE       |  P=0.351N                                          |  P=0.226N                                          |
|FISHER EXACT           |               P=0.752N     P=0.730      P=0.541N   |               P=0.691N     P=0.467      P=0.270N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  16
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 12/60 (20%)   7/60 (12%)   5/60 (8%)    1/60 (2%)  |
|ADJUSTED (b)           |                                                    |  28.5%        17.6%        14.4%         4.2%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  2/10 (20%)   1/10 (10%)   1/10 (10%)   0/7 (0%)   |
|TERMINAL (d)           |                                                    |  5/32 (16%)   4/34 (12%)   4/31 (13%)   1/24 (4%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   450 (I)      451 (I)      450 (I)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.004N**   P=0.135N     P=0.068N     P=0.009N** |
|INCIDENTAL TUMOR       |                                                    |  P=0.002N**   P=0.124N     P=0.056N     P=0.003N** |
|LOGISTIC REGRESSION    |                                                    |  P=0.001N**   P=0.157N     P=0.057N     P=0.002N** |
|COCHRAN-ARMITAGE       |                                                    |  P<0.001N**                                        |
|FISHER EXACT           |                                                    |               P=0.159N     P=0.057N     P=0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    | 13/60 (22%)   7/60 (12%)   5/60 (8%)    1/60 (2%)  |
|ADJUSTED (b)           |                                                    |  29.8%        17.6%        14.4%         4.2%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  2/10 (20%)   1/10 (10%)   1/10 (10%)   0/7 (0%)   |
|TERMINAL (d)           |                                                    |  5/32 (16%)   4/34 (12%)   4/31 (13%)   1/24 (4%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   413          451 (I)      450 (I)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.002N**   P=0.095N     P=0.046N*    P=0.006N** |
|INCIDENTAL TUMOR       |                                                    |  P=0.001N**   P=0.114N     P=0.044N*    P=0.001N** |
|LOGISTIC REGRESSION    |                                                    |  P<0.001N**   P=0.118N     P=0.037N*    P=0.001N** |
|COCHRAN-ARMITAGE       |                                                    |  P<0.001N**                                        |
|FISHER EXACT           |                                                    |               P=0.110N     P=0.036N*    P<0.001N** |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  17
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    2/60 (3%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         5.8%         4.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  0/23 (0%)    0/18 (0%)    0/11 (0%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          184          625       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.173        (e)        P=0.194      P=0.406    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.426        (e)        P=0.253      P=0.648    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.328        (e)        P=0.258      P=0.484    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.247                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.248      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 22/60 (37%)  31/60 (52%)  24/60 (40%)  19/60 (32%) | 17/60 (28%)  18/60 (30%)  13/60 (22%)   9/60 (15%) |
|ADJUSTED (b)           |  58.6%        82.1%        72.3%        64.9%      |  40.2%        41.8%        36.4%        30.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  9/23 (39%)  12/18 (67%)   5/11 (45%)   3/10 (30%) |  8/32 (25%)  10/34 (29%)   9/31 (29%)   5/24 (21%) |
|FIRST INCIDENCE (DAYS) |   512          501          479          365       |   412          479          643          499       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.145      P=0.013 *    P=0.044 *    P=0.097    |  P=0.158N     P=0.558N     P=0.299N     P=0.222N   |
|INCIDENTAL TUMOR       |  P=0.164N     P=0.035 *    P=0.544N     P=0.347N   |  P=0.042N*    P=0.351      P=0.318N     P=0.110N   |
|LOGISTIC REGRESSION    |  P=0.152N     P=0.016 *    P=0.447      P=0.502    |  P=0.058N     P=0.498N     P=0.257N     P=0.118N   |
|COCHRAN-ARMITAGE       |  P=0.142N                                          |  P=0.027N*                                         |
|FISHER EXACT           |               P=0.071      P=0.426      P=0.350N   |               P=0.500      P=0.264N     P=0.060N   |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  18
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   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)            |  0/60 (0%)    0/60 (0%)    2/60 (3%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         5.8%         4.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           |  0/23 (0%)    0/18 (0%)    0/11 (0%)    0/10 (0%)  |  0/32 (0%)    0/34 (0%)    0/31 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          184          625       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.173        (e)        P=0.194      P=0.406    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.426        (e)        P=0.253      P=0.648    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.328        (e)        P=0.258      P=0.484    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.247                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.248      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 57/60 (95%)  52/60 (87%)  54/60 (90%)  52/60 (87%) | 43/60 (72%)  37/60 (62%)  40/60 (67%)  24/60 (40%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  93.3%        80.0%        90.8%        66.8%      |
|INTERIM SACRIFICE 1 (c)|  9/10 (90%)   5/10 (50%)   7/10 (70%)   8/9 (89%)  |  4/10 (40%)   2/10 (20%)   2/10 (20%)   1/7 (14%)  |
|TERMINAL (d)           | 23/23 (100%) 18/18 (100%) 11/11 (100%) 10/10 (100%)| 29/32 (91%)  25/34 (74%)  27/31 (87%)  13/24 (54%) |
|FIRST INCIDENCE (DAYS) |   462 (I)      462 (I)      401          458       |   450 (I)      451 (I)      450 (I)      421       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.001 **   P=0.228      P=0.013 *    P=0.002 ** |  P=0.099N     P=0.098N     P=0.424N     P=0.063N   |
|INCIDENTAL TUMOR       |  P=0.477      P=0.182N     P=0.412N     P=0.672    |  P=0.004N**   P=0.026N*    P=0.267N     P=0.002N** |
|LOGISTIC REGRESSION    |  P=0.524      P=0.284N     P=0.343N     P=0.548N   |  P=0.007N**   P=0.046N*    P=0.279N     P=0.003N** |
|COCHRAN-ARMITAGE       |  P=0.150N                                          |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.102N     P=0.245N     P=0.102N   |               P=0.166N     P=0.346N     P<0.001N** |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  19
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   VEHICLE      8.3          16.6         33.3      |   VEHICLE      8.3          16.6         33.3      |
|                       |   MALE         MG/KG        MG/KG        MG/KG     |   FEMALE       MG/KG        MG/KG        MG/KG     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 28/60 (47%)  32/60 (53%)  29/60 (48%)  23/60 (38%) | 19/60 (32%)  18/60 (30%)  16/60 (27%)  16/60 (27%) |
|ADJUSTED (b)           |  69.9%        85.1%        80.2%        70.9%      |  43.6%        41.8%        44.0%        47.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |
|TERMINAL (d)           | 12/23 (52%)  13/18 (72%)   6/11 (55%)   3/10 (30%) |  9/32 (28%)  10/34 (29%)  11/31 (35%)   8/24 (33%) |
|FIRST INCIDENCE (DAYS) |   512          501          184          365       |   412          479          643          371       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.102      P=0.060      P=0.040 *    P=0.094    |  P=0.394      P=0.412N     P=0.384N     P=0.474    |
|INCIDENTAL TUMOR       |  P=0.131N     P=0.182      P=0.512N     P=0.212N   |  P=0.368N     P=0.463      P=0.442N     P=0.446N   |
|LOGISTIC REGRESSION    |  P=0.352N     P=0.113      P=0.352      P=0.343N   |  P=0.501N     P=0.449N     P=0.337N     P=0.484N   |
|COCHRAN-ARMITAGE       |  P=0.127N                                          |  P=0.290N                                          |
|FISHER EXACT           |               P=0.292      P=0.500      P=0.230N   |               P=0.500N     P=0.344N     P=0.344N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 57/60 (95%)  52/60 (87%)  57/60 (95%)  54/60 (90%) | 50/60 (83%)  44/60 (73%)  41/60 (68%)  33/60 (55%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  96.1%        86.2%        93.1%        81.6%      |
|INTERIM SACRIFICE 1 (c)|  9/10 (90%)   5/10 (50%)   7/10 (70%)   8/9 (89%)  |  4/10 (40%)   2/10 (20%)   2/10 (20%)   1/7 (14%)  |
|TERMINAL (d)           | 23/23 (100%) 18/18 (100%) 11/11 (100%) 10/10 (100%)| 30/32 (94%)  27/34 (79%)  28/31 (90%)  17/24 (71%) |
|FIRST INCIDENCE (DAYS) |   462 (I)      462 (I)      184          365       |   412          451 (I)      450 (I)      371       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.228      P=0.005 **   P<0.001 ** |  P=0.246N     P=0.110N     P=0.122N     P=0.214N   |
|INCIDENTAL TUMOR       |  P=0.241      P=0.182N     P=0.657      P=0.485    |  P=0.002N**   P=0.050N     P=0.030N*    P=0.002N** |
|LOGISTIC REGRESSION    |  P=0.192      P=0.284N     P=0.584      P=0.509    |  P=0.012N*    P=0.017N*    P=0.013N*    P=0.006N** |
|COCHRAN-ARMITAGE       |  P=0.376N                                          |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.102N     P=0.660N     P=0.245N   |               P=0.134N     P=0.043N*    P<0.001N** |
|=================================================================================================================================|
 
         DATE: 09/14/94                     EXPERIMENT: 05108 TEST: 01                                                 PAGE  20
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- PROMETHAZINE HYDROCHLORIDE
 
                                                 MALE TERMINAL SACRIFICE AT 103 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
 
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   462
          Female interim sacrifices(days): 450
 (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.