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TR 380 Rat Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                      EPINEPHRINE HCL                                   DATE: 09/12/94       
EXPERIMENT: 05095 TEST: 01                                                                                     TIME: 23:40:57       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-38061          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 55663        
PATHOLOGIST: R. RENNE                                                                                          CAS: 55-31-2         
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Battelle Northwest                                      EPINEPHRINE HCL                                   DATE: 09/12/94      
EXPERIMENT: 05095 TEST: 01                                                                                     TIME: 23:40:57      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-38061          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 55663       
PATHOLOGIST: R. RENNE                                                                                          CAS: 55-31-2        
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                      EPINEPHRINE HCL                                   DATE: 09/12/94       
EXPERIMENT: 05095 TEST: 01                                                                                     TIME: 23:40:57       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-38061          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 55663        
PATHOLOGIST: R. RENNE                                                                                          CAS: 55-31-2         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                        IN THE ANALYSIS OF THE STUDY OF EPINEPHRINE HCL
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Skin                          Fibroma
                             Thyroid Gland: C-Cell         Carcinoma
                                                           Carcinoma or Adenoma
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma or Adenoma
                             Islets, Pancreatic            Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   1
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    11/50 (22%)      3/25 (12%)     16/48 (33%)     |     1/50 (2%)       1/22 (5%)       4/47 (9%)      |
|ADJUSTED (b)           |     29.6%           37.9%           43.1%          |      2.9%            2.7%           11.0%          |
|TERMINAL (d)           |     8/33 (24%)      1/3 (33%)      11/31 (35%)     |     0/32 (0%)       0/2 (0%)        2/30 (7%)      |
|FIRST INCIDENCE (DAYS) |      661             717             556           |      715             714             581           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.110         P=0.638         P=0.142        |     P=0.125         P=0.754N        P=0.180        |
|INCIDENTAL TUMOR       |     P=0.094         P=0.553N        P=0.167        |     P=0.136         P=0.700N        P=0.198        |
|LOGISTIC REGRESSION    |     P=0.074         P=0.597         P=0.143        |     P=0.126         P=0.472         P=0.143        |
|COCHRAN-ARMITAGE       |     P=0.081                                        |     P=0.126                                        |
|FISHER EXACT           |                     P=0.236N        P=0.152        |                     P=0.521         P=0.162        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    11/50 (22%)      4/25 (16%)     17/48 (35%)     |     1/50 (2%)       1/22 (5%)       4/47 (9%)      |
|ADJUSTED (b)           |     29.6%           69.0%           44.6%          |      2.9%            2.7%           11.0%          |
|TERMINAL (d)           |     8/33 (24%)      2/3 (67%)      11/31 (35%)     |     0/32 (0%)       0/2 (0%)        2/30 (7%)      |
|FIRST INCIDENCE (DAYS) |      661             717             556           |      715             714             581           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.086         P=0.369         P=0.102        |     P=0.125         P=0.754N        P=0.180        |
|INCIDENTAL TUMOR       |     P=0.066         P=0.473         P=0.106        |     P=0.136         P=0.700N        P=0.198        |
|LOGISTIC REGRESSION    |     P=0.055         P=0.307         P=0.100        |     P=0.126         P=0.472         P=0.143        |
|COCHRAN-ARMITAGE       |     P=0.061                                        |     P=0.126                                        |
|FISHER EXACT           |                     P=0.388N        P=0.106        |                     P=0.521         P=0.162        |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   2
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/24 (4%)       0/50 (0%)      |     0/50 (0%)       1/21 (5%)       2/49 (4%)      |
|ADJUSTED (b)           |      2.1%            2.9%            0.0%          |      0.0%            0.0%            5.8%          |
|TERMINAL (d)           |     0/33 (0%)       0/1 (0%)        0/32 (0%)      |     0/32 (0%)       0/0             1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      653             693             ---           |      ---             651             662           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.388N        P=0.720         P=0.536N       |     P=0.222         P=0.500         P=0.233        |
|INCIDENTAL TUMOR       |     P=0.470N        P=0.750N        P=0.602N       |     P=0.248         P=0.557         P=0.264        |
|LOGISTIC REGRESSION    |     P=0.322N        P=0.658         P=0.475N       |     P=0.236         P=0.334         P=0.234        |
|COCHRAN-ARMITAGE       |     P=0.335N                                       |     P=0.235                                        |
|FISHER EXACT           |                     P=0.546         P=0.500N       |                     P=0.296         P=0.242        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/49 (6%)       0/25 (0%)       2/49 (4%)      |     5/48 (10%)      1/21 (5%)       0/47 (0%)      |
|ADJUSTED (b)           |      7.9%            0.0%            5.3%          |     13.6%           33.3%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/3 (0%)        1/32 (3%)      |     3/31 (10%)      1/3 (33%)       0/29 (0%)      |
|FIRST INCIDENCE (DAYS) |      707             ---             630           |      577             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.545N        P=0.280N        P=0.533N       |     P=0.030N*       P=0.583N        P=0.039N*      |
|INCIDENTAL TUMOR       |     P=0.476N        P=0.192N        P=0.392N       |     P=0.025N*       P=0.683N        P=0.030N*      |
|LOGISTIC REGRESSION    |     P=0.523N        P=0.386N        P=0.494N       |     P=0.026N*       P=0.425N        P=0.036N*      |
|COCHRAN-ARMITAGE       |     P=0.521N                                       |     P=0.027N*                                      |
|FISHER EXACT           |                     P=0.284N        P=0.500N       |                     P=0.402N        P=0.030N*      |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   3
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/49 (0%)       1/25 (4%)       2/49 (4%)      |     2/48 (4%)       1/21 (5%)       0/47 (0%)      |
|ADJUSTED (b)           |      0.0%            2.5%            5.5%          |      5.8%           33.3%            0.0%          |
|TERMINAL (d)           |     0/33 (0%)       0/3 (0%)        1/32 (3%)      |     1/31 (3%)       1/3 (33%)       0/29 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             672             672           |      682             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.204         P=0.477         P=0.224        |     P=0.184N        P=0.609         P=0.253N       |
|INCIDENTAL TUMOR       |     P=0.146         P=0.527         P=0.189        |     P=0.171N        P=0.625         P=0.225N       |
|LOGISTIC REGRESSION    |     P=0.230         P=0.409         P=0.241        |     P=0.169N        P=0.613         P=0.239N       |
|COCHRAN-ARMITAGE       |     P=0.231                                        |     P=0.176N                                       |
|FISHER EXACT           |                     P=0.338         P=0.247        |                     P=0.670         P=0.253N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/49 (6%)       1/25 (4%)       4/49 (8%)      |     7/48 (15%)      2/21 (10%)      0/47 (0%)      |
|ADJUSTED (b)           |      7.9%            2.5%           10.6%          |     18.9%           66.7%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/3 (0%)        2/32 (6%)      |     4/31 (13%)      2/3 (67%)       0/29 (0%)      |
|FIRST INCIDENCE (DAYS) |      707             672             630           |      577             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.376         P=0.540N        P=0.461        |     P=0.009N**      P=0.675         P=0.012N*      |
|INCIDENTAL TUMOR       |     P=0.380         P=0.417N        P=0.551        |     P=0.007N**      P=0.617         P=0.008N**     |
|LOGISTIC REGRESSION    |     P=0.413         P=0.637N        P=0.508        |     P=0.007N**      P=0.526N        P=0.010N*      |
|COCHRAN-ARMITAGE       |     P=0.412                                        |     P=0.008N**                                     |
|FISHER EXACT           |                     P=0.584N        P=0.500        |                     P=0.442N        P=0.007N**     |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   4
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      1/24 (4%)       1/49 (2%)      |     1/49 (2%)       1/22 (5%)       0/47 (0%)      |
|ADJUSTED (b)           |     14.4%            3.6%            2.9%          |      3.1%          100.0%            0.0%          |
|TERMINAL (d)           |     4/33 (12%)      0/1 (0%)        0/32 (0%)      |     1/32 (3%)       1/1 (100%)      0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      714             720             714           |      729 (T)         729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.096N        P=0.740N        P=0.120N       |     P=0.327N        P=0.033 *       P=0.513N       |
|INCIDENTAL TUMOR       |     P=0.124N        P=0.676N        P=0.152N       |     P=0.327N        P=0.033 *       P=0.513N       |
|LOGISTIC REGRESSION    |     P=0.098N        P=0.566         P=0.126N       |     P=0.327N        P=0.033 *       P=0.513N       |
|COCHRAN-ARMITAGE       |     P=0.093N                                       |     P=0.343N                                       |
|FISHER EXACT           |                     P=0.360N        P=0.107N       |                     P=0.527         P=0.510N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)      2/24 (8%)       1/49 (2%)      |     1/49 (2%)       1/22 (5%)       0/47 (0%)      |
|ADJUSTED (b)           |     16.4%            6.1%            2.9%          |      3.1%          100.0%            0.0%          |
|TERMINAL (d)           |     4/33 (12%)      0/1 (0%)        0/32 (0%)      |     1/32 (3%)       1/1 (100%)      0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      702             677             714           |      729 (T)         729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.060N        P=0.644         P=0.074N       |     P=0.327N        P=0.033 *       P=0.513N       |
|INCIDENTAL TUMOR       |     P=0.084N        P=0.625N        P=0.103N       |     P=0.327N        P=0.033 *       P=0.513N       |
|LOGISTIC REGRESSION    |     P=0.056N        P=0.556         P=0.073N       |     P=0.327N        P=0.033 *       P=0.513N       |
|COCHRAN-ARMITAGE       |     P=0.050N                                       |     P=0.343N                                       |
|FISHER EXACT           |                     P=0.486N        P=0.059N       |                     P=0.527         P=0.510N       |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   5
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/33 (3%)       0/49 (0%)      |     2/50 (4%)       0/31 (0%)       1/47 (2%)      |
|ADJUSTED (b)           |      3.0%            2.9%            0.0%          |      6.3%            0.0%            3.3%          |
|TERMINAL (d)           |     1/33 (3%)       0/11 (0%)       0/32 (0%)      |     2/32 (6%)       0/10 (0%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         693             ---           |      729 (T)         ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.358N        P=0.615         P=0.506N       |     P=0.488N        P=0.516N        P=0.523N       |
|INCIDENTAL TUMOR       |     P=0.395N        P=0.656         P=0.506N       |     P=0.488N        P=0.516N        P=0.523N       |
|LOGISTIC REGRESSION    |     P=0.353N        P=0.640         P=0.506N       |     P=0.488N        P=0.516N        P=0.523N       |
|COCHRAN-ARMITAGE       |     P=0.348N                                       |     P=0.516N                                       |
|FISHER EXACT           |                     P=0.640         P=0.505N       |                     P=0.378N        P=0.523N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       1/29 (3%)       2/49 (4%)      |     0/50 (0%)       1/23 (4%)       0/48 (0%)      |
|ADJUSTED (b)           |     10.7%           14.3%            5.8%          |      0.0%            2.7%            0.0%          |
|TERMINAL (d)           |     2/33 (6%)       1/7 (14%)       1/32 (3%)      |     0/32 (0%)       0/2 (0%)        0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      702             729 (T)         707           |      ---             714             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.335N        P=0.549N        P=0.376N       |     P=0.701N        P=0.511           (e)          |
|INCIDENTAL TUMOR       |     P=0.402N        P=0.476N        P=0.465N       |     P=0.665N        P=0.557           (e)          |
|LOGISTIC REGRESSION    |     P=0.343N        P=0.605N        P=0.373N       |     P=0.646N        P=0.254           (e)          |
|COCHRAN-ARMITAGE       |     P=0.330N                                       |     P=0.667N                                       |
|FISHER EXACT           |                     P=0.390N        P=0.349N       |                     P=0.315           (e)          |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   6
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      1/29 (3%)       2/49 (4%)      |     0/50 (0%)       1/23 (4%)       0/48 (0%)      |
|ADJUSTED (b)           |     13.6%           14.3%            5.8%          |      0.0%            2.7%            0.0%          |
|TERMINAL (d)           |     3/33 (9%)       1/7 (14%)       1/32 (3%)      |     0/32 (0%)       0/2 (0%)        0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      702             729 (T)         707           |      ---             714             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.221N        P=0.477N        P=0.251N       |     P=0.701N        P=0.511           (e)          |
|INCIDENTAL TUMOR       |     P=0.268N        P=0.409N        P=0.319N       |     P=0.665N        P=0.557           (e)          |
|LOGISTIC REGRESSION    |     P=0.230N        P=0.521N        P=0.251N       |     P=0.646N        P=0.254           (e)          |
|COCHRAN-ARMITAGE       |     P=0.217N                                       |     P=0.667N                                       |
|FISHER EXACT           |                     P=0.278N        P=0.226N       |                     P=0.315           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     2/50 (4%)       3/50 (6%)       4/50 (8%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      6.3%            8.8%           11.4%          |
|TERMINAL (d)           |     0/33 (0%)       0/27 (0%)       0/32 (0%)      |     2/32 (6%)       1/29 (3%)       2/30 (7%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      729 (T)         714             637           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.293         P=0.484         P=0.323        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.336         P=0.525         P=0.353        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.307         P=0.497         P=0.344        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.297                                        |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.500         P=0.339        |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   7
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |    10/50 (20%)     11/50 (22%)     11/50 (22%)     |
|ADJUSTED (b)           |      5.6%            0.0%            3.1%          |     26.9%           31.2%           30.2%          |
|TERMINAL (d)           |     1/33 (3%)       0/27 (0%)       1/32 (3%)      |     7/32 (22%)      6/29 (21%)      6/30 (20%)     |
|FIRST INCIDENCE (DAYS) |      717             ---             729 (T)       |      476             679             622           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.530N        P=0.293N        P=0.520N       |     P=0.465         P=0.446         P=0.468        |
|INCIDENTAL TUMOR       |     P=0.574N        P=0.254N        P=0.565N       |     P=0.506         P=0.501         P=0.439        |
|LOGISTIC REGRESSION    |     P=0.545N        P=0.277N        P=0.535N       |     P=0.504         P=0.487         P=0.504        |
|COCHRAN-ARMITAGE       |     P=0.528N                                       |     P=0.484                                        |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                     P=0.500         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |    11/50 (22%)     13/50 (26%)     14/50 (28%)     |
|ADJUSTED (b)           |      5.6%            0.0%            3.1%          |     29.8%           36.2%           37.5%          |
|TERMINAL (d)           |     1/33 (3%)       0/27 (0%)       1/32 (3%)      |     8/32 (25%)      7/29 (24%)      8/30 (27%)     |
|FIRST INCIDENCE (DAYS) |      717             ---             729 (T)       |      476             679             622           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.530N        P=0.293N        P=0.520N       |     P=0.305         P=0.358         P=0.298        |
|INCIDENTAL TUMOR       |     P=0.574N        P=0.254N        P=0.565N       |     P=0.342         P=0.413         P=0.269        |
|LOGISTIC REGRESSION    |     P=0.545N        P=0.277N        P=0.535N       |     P=0.335         P=0.392         P=0.328        |
|COCHRAN-ARMITAGE       |     P=0.528N                                       |     P=0.314                                        |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                     P=0.408         P=0.322        |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   8
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Granulosa Cell Tumor Malignant                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     2/50 (4%)       0/22 (0%)       0/47 (0%)      |
|ADJUSTED (b)           |                                                    |      5.9%            0.0%            0.0%          |
|TERMINAL (d)           |                                                    |     1/32 (3%)       0/1 (0%)        0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      714             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.193N        P=0.467N        P=0.247N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.181N        P=0.423N        P=0.224N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.182N        P=0.600N        P=0.238N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.195N                                       |
|FISHER EXACT           |                                                    |                     P=0.479N        P=0.263N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Granulosa Cell Tumor, Benign, Malignant, NOS                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     2/50 (4%)       1/22 (5%)       0/47 (0%)      |
|ADJUSTED (b)           |                                                    |      5.9%          100.0%            0.0%          |
|TERMINAL (d)           |                                                    |     1/32 (3%)       1/1 (100%)      0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      714             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.180N        P=0.553         P=0.247N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.171N        P=0.595         P=0.224N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.166N        P=0.503         P=0.238N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.185N                                       |
|FISHER EXACT           |                                                    |                     P=0.671         P=0.263N       |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE   9
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    34/50 (68%)     29/36 (81%)     25/48 (52%)     |    30/49 (61%)     25/38 (66%)     32/47 (68%)     |
|ADJUSTED (b)           |     76.8%          100.0%           61.2%          |     74.8%           86.9%           83.8%          |
|TERMINAL (d)           |    23/33 (70%)     14/14 (100%)    16/31 (52%)     |    22/32 (69%)     14/17 (82%)     23/29 (79%)     |
|FIRST INCIDENCE (DAYS) |      540             601             560           |      582             430             622           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.074N        P=0.021 *       P=0.168N       |     P=0.343         P=0.170         P=0.278        |
|INCIDENTAL TUMOR       |     P=0.028N*       P=0.039 *       P=0.057N       |     P=0.392         P=0.243         P=0.412        |
|LOGISTIC REGRESSION    |     P=0.031N*       P=0.049 *       P=0.084N       |     P=0.447         P=0.258         P=0.405        |
|COCHRAN-ARMITAGE       |     P=0.028N*                                      |     P=0.302                                        |
|FISHER EXACT           |                     P=0.147         P=0.080N       |                     P=0.416         P=0.313        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    34/50 (68%)     30/36 (83%)     25/48 (52%)     |    31/49 (63%)     26/38 (68%)     33/47 (70%)     |
|ADJUSTED (b)           |     76.8%          100.0%           61.2%          |     75.4%           87.2%           84.2%          |
|TERMINAL (d)           |    23/33 (70%)     14/14 (100%)    16/31 (52%)     |    22/32 (69%)     14/17 (82%)     23/29 (79%)     |
|FIRST INCIDENCE (DAYS) |      540             598             560           |      582             430             622           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.070N        P=0.015 *       P=0.168N       |     P=0.348         P=0.178         P=0.286        |
|INCIDENTAL TUMOR       |     P=0.018N*       P=0.039 *       P=0.057N       |     P=0.412         P=0.244         P=0.432        |
|LOGISTIC REGRESSION    |     P=0.026N*       P=0.035 *       P=0.084N       |     P=0.451         P=0.238         P=0.407        |
|COCHRAN-ARMITAGE       |     P=0.024N*                                      |     P=0.301                                        |
|FISHER EXACT           |                     P=0.086         P=0.080N       |                     P=0.393         P=0.307        |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  10
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      0/50 (0%)       1/50 (2%)      |     1/50 (2%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |     13.0%            0.0%            2.6%          |      2.1%            3.4%            2.6%          |
|TERMINAL (d)           |     2/33 (6%)       0/27 (0%)       0/32 (0%)      |     0/32 (0%)       1/29 (3%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      693             ---             674           |      577             729 (T)         679           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.126N        P=0.061N        P=0.132N       |     P=0.683N        P=0.739         P=0.755N       |
|INCIDENTAL TUMOR       |     P=0.169N        P=0.037N*       P=0.195N       |     P=0.642N        P=0.704         P=0.711N       |
|LOGISTIC REGRESSION    |     P=0.113N        P=0.041N*       P=0.108N       |     P=0.678         P=0.756N        P=0.739        |
|COCHRAN-ARMITAGE       |     P=0.107N                                       |     P=0.687                                        |
|FISHER EXACT           |                     P=0.028N*       P=0.102N       |                     P=0.753N        P=0.753N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.6%            0.0%            2.9%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/27 (0%)       0/32 (0%)      |     0/32 (0%)       0/29 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      717             ---             717           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.537N        P=0.293N        P=0.529N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.629N        P=0.254N        P=0.621N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.547N        P=0.277N        P=0.531N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.528N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  11
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Papilloma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            5.5%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/33 (0%)       0/27 (0%)       1/32 (3%)      |     0/32 (0%)       0/29 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             672           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.092           (e)           P=0.224        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.064           (e)           P=0.182        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.092           (e)           P=0.240        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.092                                        |       (e)                                          |
|FISHER EXACT           |                       (e)           P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            5.5%          |      3.1%            0.0%            0.0%          |
|TERMINAL (d)           |     0/33 (0%)       0/27 (0%)       1/32 (3%)      |     1/32 (3%)       0/29 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             672           |      729 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.092           (e)           P=0.224        |     P=0.429N        P=0.520N        P=0.513N       |
|INCIDENTAL TUMOR       |     P=0.064           (e)           P=0.182        |     P=0.429N        P=0.520N        P=0.513N       |
|LOGISTIC REGRESSION    |     P=0.092           (e)           P=0.240        |     P=0.429N        P=0.520N        P=0.513N       |
|COCHRAN-ARMITAGE       |     P=0.092                                        |     P=0.421N                                       |
|FISHER EXACT           |                       (e)           P=0.247        |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  12
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       4/50 (8%)      |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      8.5%            0.0%           11.3%          |      3.1%            0.0%            0.0%          |
|TERMINAL (d)           |     2/33 (6%)       0/27 (0%)       2/32 (6%)      |     1/32 (3%)       0/29 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      717             ---             672           |      729 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.282         P=0.165N        P=0.465        |     P=0.429N        P=0.520N        P=0.513N       |
|INCIDENTAL TUMOR       |     P=0.205         P=0.143N        P=0.374        |     P=0.429N        P=0.520N        P=0.513N       |
|LOGISTIC REGRESSION    |     P=0.262         P=0.158N        P=0.462        |     P=0.429N        P=0.520N        P=0.513N       |
|COCHRAN-ARMITAGE       |     P=0.284                                        |     P=0.421N                                       |
|FISHER EXACT           |                     P=0.121N        P=0.500        |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    39/50 (78%)     32/47 (68%)     42/50 (84%)     |                                                    |
|ADJUSTED (b)           |     86.6%           96.8%           93.2%          |                                                    |
|TERMINAL (d)           |    27/33 (82%)     23/24 (96%)     29/32 (91%)     |                                                    |
|FIRST INCIDENCE (DAYS) |      653             535             500           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.224         P=0.345         P=0.235        |                                                    |
|INCIDENTAL TUMOR       |     P=0.085         P=0.564N        P=0.204        |                                                    |
|LOGISTIC REGRESSION    |     P=0.051         P=0.561         P=0.192        |                                                    |
|COCHRAN-ARMITAGE       |     P=0.180                                        |                                                    |
|FISHER EXACT           |                     P=0.192N        P=0.306        |                                                    |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  13
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     9/50 (18%)      3/24 (13%)      5/49 (10%)     |     4/50 (8%)       3/21 (14%)      5/47 (11%)     |
|ADJUSTED (b)           |     24.4%            8.8%           15.6%          |     12.5%            0.0%           15.8%          |
|TERMINAL (d)           |     7/33 (21%)      0/2 (0%)        5/32 (16%)     |     4/32 (13%)      0/0             4/30 (13%)     |
|FIRST INCIDENCE (DAYS) |      463             681             729 (T)       |      729 (T)         623             715           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.178N        P=0.563         P=0.215N       |     P=0.516         P=0.128         P=0.466        |
|INCIDENTAL TUMOR       |     P=0.268N        P=0.598         P=0.317N       |     P=0.536         P=0.127         P=0.478        |
|LOGISTIC REGRESSION    |     P=0.239N        P=0.340N        P=0.201N       |     P=0.539         P=0.180         P=0.497        |
|COCHRAN-ARMITAGE       |     P=0.192N                                       |     P=0.466                                        |
|FISHER EXACT           |                     P=0.407N        P=0.205N       |                     P=0.339         P=0.460        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       2/24 (8%)       0/49 (0%)      |     2/50 (4%)       0/21 (0%)       2/47 (4%)      |
|ADJUSTED (b)           |      9.9%          100.0%            0.0%          |      6.3%            0.0%            6.7%          |
|TERMINAL (d)           |     1/33 (3%)       2/2 (100%)      0/32 (0%)      |     2/32 (6%)       0/0             2/30 (7%)      |
|FIRST INCIDENCE (DAYS) |      540             729 (T)         ---           |      729 (T)         ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.055N        P=0.513         P=0.075N       |     P=0.615           (e)           P=0.673        |
|INCIDENTAL TUMOR       |     P=0.097N        P=0.516         P=0.187N       |     P=0.615           (e)           P=0.673        |
|LOGISTIC REGRESSION    |     P=0.048N*       P=0.674N        P=0.058N       |     P=0.615           (e)           P=0.673        |
|COCHRAN-ARMITAGE       |     P=0.050N*                                      |     P=0.569                                        |
|FISHER EXACT           |                     P=0.640         P=0.061N       |                     P=0.493N        P=0.668        |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  14
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    13/50 (26%)      5/24 (21%)      5/49 (10%)     |     5/50 (10%)      3/21 (14%)      7/47 (15%)     |
|ADJUSTED (b)           |     32.4%          100.0%           15.6%          |     15.6%            0.0%           22.3%          |
|TERMINAL (d)           |     8/33 (24%)      2/2 (100%)      5/32 (16%)     |     5/32 (16%)      0/0             6/30 (20%)     |
|FIRST INCIDENCE (DAYS) |      463             681             729 (T)       |      729 (T)         623             715           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.033N*       P=0.430         P=0.047N*      |     P=0.389         P=0.128         P=0.337        |
|INCIDENTAL TUMOR       |     P=0.077N        P=0.452         P=0.132N       |     P=0.406         P=0.127         P=0.347        |
|LOGISTIC REGRESSION    |     P=0.032N*       P=0.353N        P=0.032N*      |     P=0.407         P=0.236         P=0.372        |
|COCHRAN-ARMITAGE       |     P=0.032N*                                      |     P=0.320                                        |
|FISHER EXACT           |                     P=0.430N        P=0.037N*      |                     P=0.439         P=0.336        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/24 (0%)       0/49 (0%)      |     0/50 (0%)       0/21 (0%)       0/47 (0%)      |
|ADJUSTED (b)           |      5.6%            0.0%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       0/2 (0%)        0/32 (0%)      |     0/32 (0%)       0/0             0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      717             ---             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.196N        P=0.507N        P=0.255N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.219N        P=0.447N        P=0.299N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.198N        P=0.681N        P=0.259N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.189N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.454N        P=0.253N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  15
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Papilloma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/22 (0%)       0/49 (0%)      |     2/49 (4%)       0/21 (0%)       0/47 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      6.3%            0.0%            0.0%          |
|TERMINAL (d)           |     0/33 (0%)       0/1 (0%)        0/32 (0%)      |     2/32 (6%)       0/0             0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      729 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.189N          (e)           P=0.252N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.189N          (e)           P=0.252N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.189N          (e)           P=0.252N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.191N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.487N        P=0.258N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)      4/50 (8%)       4/50 (8%)      |
|ADJUSTED (b)           |                                                    |     28.4%           12.8%           13.3%          |
|TERMINAL (d)           |                                                    |     7/32 (22%)      3/29 (10%)      4/30 (13%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      693             714             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.102N        P=0.097N        P=0.092N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.083N        P=0.070N        P=0.070N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.083N        P=0.072N        P=0.069N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.089N                                       |
|FISHER EXACT           |                                                    |                     P=0.074N        P=0.074N       |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  16
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)      4/50 (8%)       4/50 (8%)      |
|ADJUSTED (b)           |                                                    |     28.4%           12.8%           13.3%          |
|TERMINAL (d)           |                                                    |     7/32 (22%)      3/29 (10%)      4/30 (13%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      693             714             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.102N        P=0.097N        P=0.092N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.083N        P=0.070N        P=0.070N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.083N        P=0.072N        P=0.069N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.089N                                       |
|FISHER EXACT           |                                                    |                     P=0.074N        P=0.074N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    19/50 (38%)     21/50 (42%)     22/50 (44%)     |    24/50 (48%)     18/50 (36%)     16/50 (32%)     |
|ADJUSTED (b)           |     47.4%           50.4%           50.3%          |     52.6%           40.9%           41.4%          |
|TERMINAL (d)           |    13/33 (39%)      8/27 (30%)     11/32 (34%)     |    11/32 (34%)      4/29 (14%)      9/30 (30%)     |
|FIRST INCIDENCE (DAYS) |      463             535             556           |      258             126             615           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.325         P=0.215         P=0.288        |     P=0.136N        P=0.245N        P=0.131N       |
|INCIDENTAL TUMOR       |     P=0.364         P=0.474         P=0.462        |     P=0.059N        P=0.063N        P=0.094N       |
|LOGISTIC REGRESSION    |     P=0.384         P=0.500         P=0.382        |     P=0.102N        P=0.131N        P=0.086N       |
|COCHRAN-ARMITAGE       |     P=0.334                                        |     P=0.088N                                       |
|FISHER EXACT           |                     P=0.419         P=0.342        |                     P=0.156N        P=0.076N       |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  17
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       3/50 (6%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      3.0%            5.9%            8.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/33 (3%)       1/27 (4%)       1/32 (3%)      |     0/32 (0%)       0/29 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         644             556           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.264         P=0.444         P=0.304        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.418         P=0.717         P=0.435        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.281         P=0.506         P=0.331        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.259                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.309        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    50/50 (100%)    47/50 (94%)     50/50 (100%)    |    43/50 (86%)     35/50 (70%)     38/50 (76%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     95.5%           77.6%           88.2%          |
|TERMINAL (d)           |    33/33 (100%)    27/27 (100%)    32/32 (100%)    |    30/32 (94%)     19/29 (66%)     25/30 (83%)     |
|FIRST INCIDENCE (DAYS) |      463             535             500           |      476             430             581           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.433         P=0.186         P=0.386        |     P=0.380N        P=0.230N        P=0.339N       |
|INCIDENTAL TUMOR       |     P=0.062           (e)             (e)          |     P=0.279N        P=0.035N*       P=0.198N       |
|LOGISTIC REGRESSION    |     P=0.417         P=0.094N          (e)          |     P=0.189N        P=0.050N        P=0.098N       |
|COCHRAN-ARMITAGE       |     P=0.472                                        |     P=0.255N                                       |
|FISHER EXACT           |                     P=0.121N        P=1.000N       |                     P=0.045N*       P=0.154N       |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  18
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         1.5MG/M3        5.0MG/M3      |      CONTROL         1.5MG/M3        5.0MG/M3      |
|                       |      MALE            MALE            MALE          |      FEMALE          FEMALE          FEMALE        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    25/50 (50%)     27/50 (54%)     26/50 (52%)     |    29/50 (58%)     22/50 (44%)     23/50 (46%)     |
|ADJUSTED (b)           |     58.4%           61.2%           58.7%          |     62.6%           48.5%           56.2%          |
|TERMINAL (d)           |    16/33 (48%)     11/27 (41%)     14/32 (44%)     |    15/32 (47%)      6/29 (21%)     13/30 (43%)     |
|FIRST INCIDENCE (DAYS) |      463             535             556           |      258             126             615           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.465         P=0.189         P=0.410        |     P=0.273N        P=0.224N        P=0.249N       |
|INCIDENTAL TUMOR       |     P=0.503         P=0.490         P=0.531        |     P=0.169N        P=0.036N*       P=0.171N       |
|LOGISTIC REGRESSION    |     P=0.543N        P=0.567         P=0.543        |     P=0.224N        P=0.098N        P=0.167N       |
|COCHRAN-ARMITAGE       |     P=0.508                                        |     P=0.205N                                       |
|FISHER EXACT           |                     P=0.421         P=0.500        |                     P=0.115N        P=0.158N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    50/50 (100%)    49/50 (98%)     50/50 (100%)    |    49/50 (98%)     41/50 (82%)     43/50 (86%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     98.0%           82.0%           91.5%          |
|TERMINAL (d)           |    33/33 (100%)    27/27 (100%)    32/32 (100%)    |    31/32 (97%)     20/29 (69%)     26/30 (87%)     |
|FIRST INCIDENCE (DAYS) |      463             535             500           |      258             126             581           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.464         P=0.115         P=0.386        |     P=0.325N        P=0.261N        P=0.296N       |
|INCIDENTAL TUMOR       |     P=0.443           (e)             (e)          |     P=0.111N        P=0.005N**      P=0.034N*      |
|LOGISTIC REGRESSION    |     P=0.676         P=0.465N          (e)          |     P=0.113N        P=0.005N**      P=0.023N*      |
|COCHRAN-ARMITAGE       |     P=0.698                                        |     P=0.111N                                       |
|FISHER EXACT           |                     P=0.500N        P=1.000N       |                     P=0.008N**      P=0.030N*      |
|=================================================================================================================================|
 
         DATE: 09/13/94                     EXPERIMENT: 05095 TEST: 01                                                 PAGE  19
                             STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- EPINEPHRINE HCL
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
 
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).

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