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TR 387 Rat Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Microbiological Assoc.                              DL AMPHETAMINE SULFATE                                DATE: 09/04/94       
EXPERIMENT: 05029 TEST: 01                                                                                     TIME: 11:18:15       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01CP9565001          ROUTE: DOSED FEED                                                                  NTP C#: 55710        
PATHOLOGIST: R. KOVATCH                                                                                        CAS: 60-13-9         
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Microbiological Assoc.                              DL AMPHETAMINE SULFATE                                DATE: 09/04/94      
EXPERIMENT: 05029 TEST: 01                                                                                     TIME: 11:18:15      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01CP9565001          ROUTE: DOSED FEED                                                                  NTP C#: 55710       
PATHOLOGIST: R. KOVATCH                                                                                        CAS: 60-13-9        
 
 
 
 
 
                                                    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: Microbiological Assoc.                              DL AMPHETAMINE SULFATE                                DATE: 09/04/94       
EXPERIMENT: 05029 TEST: 01                                                                                     TIME: 11:18:15       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01CP9565001          ROUTE: DOSED FEED                                                                  NTP C#: 55710        
PATHOLOGIST: R. KOVATCH                                                                                        CAS: 60-13-9         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                     IN THE ANALYSIS OF THE STUDY OF DL AMPHETAMINE SULFATE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Testes                        Adenoma
                             Thyroid Gland: C-Cell         Carcinoma or Adenoma
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Mammary Gland                 Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Skin: Subcutaneous Tissue     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                             Uterus                        Polyp Stromal
                                                           Sarcoma Stromal or Polyp Stromal
                             All Organs                    Benign Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   1
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/49 (0%)       0/48 (0%)       1/50 (2%)      |     0/50 (0%)       2/48 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            3.0%          |      0.0%            5.0%            0.0%          |
|TERMINAL (d)           |     0/29 (0%)       0/30 (0%)       1/33 (3%)      |     0/33 (0%)       2/40 (5%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             729 (T)       |      ---             731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.344           (e)           P=0.526        |     P=0.488N        P=0.282           (e)          |
|INCIDENTAL TUMOR       |     P=0.344           (e)           P=0.526        |     P=0.488N        P=0.282           (e)          |
|LOGISTIC REGRESSION    |     P=0.344           (e)           P=0.526        |     P=0.488N        P=0.282           (e)          |
|COCHRAN-ARMITAGE       |     P=0.327                                        |     P=0.496N                                       |
|FISHER EXACT           |                       (e)           P=0.505        |                     P=0.237           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    23/49 (47%)     15/44 (34%)      6/50 (12%)     |     2/49 (4%)       4/47 (9%)       2/49 (4%)      |
|ADJUSTED (b)           |     59.5%           50.2%           16.7%          |      6.3%            9.7%            5.2%          |
|TERMINAL (d)           |    14/29 (48%)     12/26 (46%)      4/33 (12%)     |     2/32 (6%)       3/39 (8%)       1/37 (3%)      |
|FIRST INCIDENCE (DAYS) |      579             655             666           |      731 (T)         666             710           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001N**      P=0.143N        P<0.001N**     |     P=0.469N        P=0.419         P=0.649N       |
|INCIDENTAL TUMOR       |     P<0.001N**      P=0.155N        P<0.001N**     |     P=0.507N        P=0.315         P=0.687        |
|LOGISTIC REGRESSION    |     P<0.001N**      P=0.204N        P<0.001N**     |     P=0.491N        P=0.341         P=0.676N       |
|COCHRAN-ARMITAGE       |     P<0.001N**                                     |     P=0.493N                                       |
|FISHER EXACT           |                     P=0.147N        P<0.001N**     |                     P=0.319         P=0.691N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   2
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    23/49 (47%)     15/44 (34%)      7/50 (14%)     |     2/49 (4%)       4/47 (9%)       2/49 (4%)      |
|ADJUSTED (b)           |     59.5%           50.2%           19.6%          |      6.3%            9.7%            5.2%          |
|TERMINAL (d)           |    14/29 (48%)     12/26 (46%)      5/33 (15%)     |     2/32 (6%)       3/39 (8%)       1/37 (3%)      |
|FIRST INCIDENCE (DAYS) |      579             655             666           |      731 (T)         666             710           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001N**      P=0.143N        P<0.001N**     |     P=0.469N        P=0.419         P=0.649N       |
|INCIDENTAL TUMOR       |     P<0.001N**      P=0.155N        P<0.001N**     |     P=0.507N        P=0.315         P=0.687        |
|LOGISTIC REGRESSION    |     P<0.001N**      P=0.204N        P<0.001N**     |     P=0.491N        P=0.341         P=0.676N       |
|COCHRAN-ARMITAGE       |     P<0.001N**                                     |     P=0.493N                                       |
|FISHER EXACT           |                     P=0.147N        P<0.001N**     |                     P=0.319         P=0.691N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/48 (4%)       5/47 (11%)      1/49 (2%)      |     2/39 (5%)       1/37 (3%)       0/39 (0%)      |
|ADJUSTED (b)           |      6.7%           15.9%            3.0%          |      7.0%            3.3%            0.0%          |
|TERMINAL (d)           |     2/30 (7%)       4/29 (14%)      1/33 (3%)      |     1/24 (4%)       1/30 (3%)       0/29 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         660             729 (T)       |      726             731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.214N        P=0.206         P=0.467N       |     P=0.192N        P=0.424N        P=0.210N       |
|INCIDENTAL TUMOR       |     P=0.224N        P=0.205         P=0.467N       |     P=0.217N        P=0.577N        P=0.272N       |
|LOGISTIC REGRESSION    |     P=0.225N        P=0.180         P=0.467N       |     P=0.194N        P=0.462N        P=0.216N       |
|COCHRAN-ARMITAGE       |     P=0.240N                                       |     P=0.206N                                       |
|FISHER EXACT           |                     P=0.209         P=0.492N       |                     P=0.520N        P=0.247N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   3
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/48 (0%)       1/47 (2%)       2/49 (4%)      |     0/39 (0%)       0/37 (0%)       0/39 (0%)      |
|ADJUSTED (b)           |      0.0%            2.4%            6.1%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/30 (0%)       0/29 (0%)       2/33 (6%)      |     0/24 (0%)       0/30 (0%)       0/29 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             655             729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.232         P=0.505         P=0.259        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.211         P=0.500         P=0.259        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.221         P=0.520         P=0.259        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.217                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.495         P=0.253        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/48 (4%)       6/47 (13%)      3/49 (6%)      |     2/39 (5%)       1/37 (3%)       0/39 (0%)      |
|ADJUSTED (b)           |      6.7%           17.9%            9.1%          |      7.0%            3.3%            0.0%          |
|TERMINAL (d)           |     2/30 (7%)       4/29 (14%)      3/33 (9%)      |     1/24 (4%)       1/30 (3%)       0/29 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         655             729 (T)       |      726             731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.499N        P=0.130         P=0.544        |     P=0.192N        P=0.424N        P=0.210N       |
|INCIDENTAL TUMOR       |     P=0.526N        P=0.127         P=0.544        |     P=0.217N        P=0.577N        P=0.272N       |
|LOGISTIC REGRESSION    |     P=0.522N        P=0.107         P=0.544        |     P=0.194N        P=0.462N        P=0.216N       |
|COCHRAN-ARMITAGE       |     P=0.540N                                       |     P=0.206N                                       |
|FISHER EXACT           |                     P=0.127         P=0.510        |                     P=0.520N        P=0.247N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   4
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/47 (2%)       2/50 (4%)      |     1/50 (2%)       1/48 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      3.3%            3.2%            6.1%          |      3.0%            2.5%            0.0%          |
|TERMINAL (d)           |     1/30 (3%)       1/31 (3%)       2/33 (6%)      |     1/33 (3%)       1/40 (3%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         729 (T)       |      731 (T)         731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.439         P=0.755N        P=0.533        |     P=0.359N        P=0.718N        P=0.477N       |
|INCIDENTAL TUMOR       |     P=0.439         P=0.755N        P=0.533        |     P=0.359N        P=0.718N        P=0.477N       |
|LOGISTIC REGRESSION    |     P=0.439         P=0.755N        P=0.533        |     P=0.359N        P=0.718N        P=0.477N       |
|COCHRAN-ARMITAGE       |     P=0.415                                        |     P=0.368N                                       |
|FISHER EXACT           |                     P=0.737         P=0.500        |                     P=0.742         P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       2/47 (4%)       3/50 (6%)      |     1/50 (2%)       1/48 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      6.7%            6.2%            8.7%          |      3.0%            2.5%            0.0%          |
|TERMINAL (d)           |     2/30 (7%)       1/31 (3%)       2/33 (6%)      |     1/33 (3%)       1/40 (3%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         705             722           |      731 (T)         731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.471         P=0.688N        P=0.543        |     P=0.359N        P=0.718N        P=0.477N       |
|INCIDENTAL TUMOR       |     P=0.436         P=0.693N        P=0.516        |     P=0.359N        P=0.718N        P=0.477N       |
|LOGISTIC REGRESSION    |     P=0.461         P=0.679         P=0.533        |     P=0.359N        P=0.718N        P=0.477N       |
|COCHRAN-ARMITAGE       |     P=0.439                                        |     P=0.368N                                       |
|FISHER EXACT           |                     P=0.668         P=0.500        |                     P=0.742         P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   5
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       2/50 (4%)       2/50 (4%)      |     0/50 (0%)       3/50 (6%)       2/50 (4%)      |
|ADJUSTED (b)           |      9.2%            5.6%            6.1%          |      0.0%            7.1%            5.2%          |
|TERMINAL (d)           |     1/30 (3%)       1/31 (3%)       2/33 (6%)      |     0/33 (0%)       3/42 (7%)       1/37 (3%)      |
|FIRST INCIDENCE (DAYS) |      708             660             729 (T)       |      ---             731 (T)         710           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.463N        P=0.497N        P=0.461N       |     P=0.426         P=0.167         P=0.258        |
|INCIDENTAL TUMOR       |     P=0.517N        P=0.494N        P=0.510N       |     P=0.403         P=0.167         P=0.193        |
|LOGISTIC REGRESSION    |     P=0.483N        P=0.516N        P=0.478N       |     P=0.415         P=0.167         P=0.239        |
|COCHRAN-ARMITAGE       |     P=0.500N                                       |     P=0.417                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.121         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            9.7%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/30 (0%)       3/31 (10%)      0/33 (0%)      |     0/33 (0%)       0/42 (0%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             729 (T)         ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.368N        P=0.126           (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.368N        P=0.126           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.368N        P=0.126           (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.394N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.121           (e)          |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   6
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       5/50 (10%)      2/50 (4%)      |     0/50 (0%)       3/50 (6%)       2/50 (4%)      |
|ADJUSTED (b)           |      9.2%           15.0%            6.1%          |      0.0%            7.1%            5.2%          |
|TERMINAL (d)           |     1/30 (3%)       4/31 (13%)      2/33 (6%)      |     0/33 (0%)       3/42 (7%)       1/37 (3%)      |
|FIRST INCIDENCE (DAYS) |      708             660             729 (T)       |      ---             731 (T)         710           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.287N        P=0.368         P=0.461N       |     P=0.426         P=0.167         P=0.258        |
|INCIDENTAL TUMOR       |     P=0.323N        P=0.368         P=0.510N       |     P=0.403         P=0.167         P=0.193        |
|LOGISTIC REGRESSION    |     P=0.303N        P=0.338         P=0.478N       |     P=0.415         P=0.167         P=0.239        |
|COCHRAN-ARMITAGE       |     P=0.325N                                       |     P=0.417                                        |
|FISHER EXACT           |                     P=0.357         P=0.500N       |                     P=0.121         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      6.1%            2.4%            0.0%          |
|TERMINAL (d)           |     0/30 (0%)       0/31 (0%)       0/33 (0%)      |     2/33 (6%)       1/42 (2%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      731 (T)         731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.199N        P=0.416N        P=0.213N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.199N        P=0.416N        P=0.213N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.199N        P=0.416N        P=0.213N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.209N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.500N        P=0.247N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   7
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     3/50 (6%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      7.4%            2.4%            2.7%          |
|TERMINAL (d)           |     0/30 (0%)       0/31 (0%)       0/33 (0%)      |     1/33 (3%)       1/42 (2%)       1/37 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      547             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.336N        P=0.259N        P=0.292N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.406N        P=0.301N        P=0.395N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.321N        P=0.316N        P=0.287N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.337N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.309N        P=0.309N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     5/50 (10%)      2/50 (4%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |     13.2%            4.8%            2.7%          |
|TERMINAL (d)           |     0/30 (0%)       0/31 (0%)       0/33 (0%)      |     3/33 (9%)       2/42 (5%)       1/37 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      547             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.116N        P=0.153N        P=0.092N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.143N        P=0.174N        P=0.134N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.119N        P=0.223N        P=0.101N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.120N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.218N        P=0.102N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   8
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       0/50 (0%)      |    21/50 (42%)     11/50 (22%)      2/50 (4%)      |
|ADJUSTED (b)           |     10.0%            0.0%            0.0%          |     51.0%           26.2%            5.4%          |
|TERMINAL (d)           |     3/30 (10%)      0/31 (0%)       0/33 (0%)      |    13/33 (39%)     11/42 (26%)      2/37 (5%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             ---           |      666             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.127N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.006N**      P<0.001N**     |
|INCIDENTAL TUMOR       |     P=0.127N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.052N        P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.126N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.014N*       P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.140N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.121N        P=0.121N       |                     P=0.026N*       P<0.001N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       0/50 (0%)      |    23/50 (46%)     11/50 (22%)      2/50 (4%)      |
|ADJUSTED (b)           |     10.0%            0.0%            0.0%          |     55.9%           26.2%            5.4%          |
|TERMINAL (d)           |     3/30 (10%)      0/31 (0%)       0/33 (0%)      |    15/33 (45%)     11/42 (26%)      2/37 (5%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             ---           |      666             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.127N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.002N**      P<0.001N**     |
|INCIDENTAL TUMOR       |     P=0.127N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.017N*       P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.126N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.004N**      P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.140N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.121N        P=0.121N       |                     P=0.010N**      P<0.001N**     |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE   9
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       0/50 (0%)      |    25/50 (50%)     12/50 (24%)      3/50 (6%)      |
|ADJUSTED (b)           |     10.0%            0.0%            0.0%          |     59.3%           28.6%            8.1%          |
|TERMINAL (d)           |     3/30 (10%)      0/31 (0%)       0/33 (0%)      |    16/33 (48%)     12/42 (29%)      3/37 (8%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             ---           |      547             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.127N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.001N**      P<0.001N**     |
|INCIDENTAL TUMOR       |     P=0.127N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.009N**      P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.126N        P=0.114N        P=0.104N       |     P<0.001N**      P=0.003N**      P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.140N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.121N        P=0.121N       |                     P=0.006N**      P<0.001N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.8%            2.2%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/30 (0%)       0/31 (0%)       0/33 (0%)      |     0/33 (0%)       0/42 (0%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      637             524             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.211N        P=0.510N        P=0.240N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.219N        P=0.518N        P=0.283N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.226N        P=0.440N        P=0.245N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.209N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  10
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/49 (31%)     15/48 (31%)      9/49 (18%)     |    31/50 (62%)     24/48 (50%)     19/50 (38%)     |
|ADJUSTED (b)           |     43.1%           44.7%           25.4%          |     77.0%           55.4%           45.0%          |
|TERMINAL (d)           |    11/30 (37%)     12/30 (40%)      7/33 (21%)     |    24/33 (73%)     21/40 (53%)     14/37 (38%)     |
|FIRST INCIDENCE (DAYS) |      533             660             660           |      541             340             504           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.052N        P=0.579         P=0.085N       |     P=0.017N*       P=0.021N*       P=0.007N**     |
|INCIDENTAL TUMOR       |     P=0.061N        P=0.582N        P=0.097N       |     P=0.018N*       P=0.036N*       P=0.016N*      |
|LOGISTIC REGRESSION    |     P=0.059N        P=0.526         P=0.103N       |     P=0.020N*       P=0.150N        P=0.015N*      |
|COCHRAN-ARMITAGE       |     P=0.080N                                       |     P=0.017N*                                      |
|FISHER EXACT           |                     P=0.560         P=0.120N       |                     P=0.160N        P=0.014N*      |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/49 (0%)       0/48 (0%)       0/49 (0%)      |     0/50 (0%)       2/48 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      0.0%            4.6%            0.0%          |
|TERMINAL (d)           |     0/30 (0%)       0/30 (0%)       0/33 (0%)      |     0/33 (0%)       1/40 (3%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      ---             624             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.499N        P=0.266           (e)          |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.599N        P=0.339           (e)          |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.482N        P=0.223           (e)          |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.496N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.237           (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  11
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/49 (31%)     15/48 (31%)      9/49 (18%)     |    31/50 (62%)     26/48 (54%)     19/50 (38%)     |
|ADJUSTED (b)           |     43.1%           44.7%           25.4%          |     77.0%           58.7%           45.0%          |
|TERMINAL (d)           |    11/30 (37%)     12/30 (40%)      7/33 (21%)     |    24/33 (73%)     22/40 (55%)     14/37 (38%)     |
|FIRST INCIDENCE (DAYS) |      533             660             660           |      541             340             504           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.052N        P=0.579         P=0.085N       |     P=0.013N*       P=0.049N*       P=0.007N**     |
|INCIDENTAL TUMOR       |     P=0.061N        P=0.582N        P=0.097N       |     P=0.014N*       P=0.070N        P=0.016N*      |
|LOGISTIC REGRESSION    |     P=0.059N        P=0.526         P=0.103N       |     P=0.013N*       P=0.271N        P=0.015N*      |
|COCHRAN-ARMITAGE       |     P=0.080N                                       |     P=0.011N*                                      |
|FISHER EXACT           |                     P=0.560         P=0.120N       |                     P=0.281N        P=0.014N*      |
|=================================================================================================================================|
|                                                                                                                                 |
|Salivary Glands                                                                                                                  |
|     Schwannoma Malignant                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/48 (0%)       2/50 (4%)      |     0/48 (0%)       0/49 (0%)       1/49 (2%)      |
|ADJUSTED (b)           |      3.3%            0.0%            4.9%          |      0.0%            0.0%            2.8%          |
|TERMINAL (d)           |     1/30 (3%)       0/30 (0%)       0/33 (0%)      |     0/31 (0%)       0/41 (0%)       1/36 (3%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             627           |      ---             ---             731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.318         P=0.500N        P=0.521        |     P=0.327           (e)           P=0.530        |
|INCIDENTAL TUMOR       |     P=0.302         P=0.500N        P=0.467        |     P=0.327           (e)           P=0.530        |
|LOGISTIC REGRESSION    |     P=0.299         P=0.500N        P=0.499        |     P=0.327           (e)           P=0.530        |
|COCHRAN-ARMITAGE       |     P=0.299                                        |     P=0.324                                        |
|FISHER EXACT           |                     P=0.510N        P=0.500        |                       (e)           P=0.505        |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  12
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       4/50 (8%)       2/50 (4%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      6.7%           11.9%            5.5%          |      2.6%            2.4%            0.0%          |
|TERMINAL (d)           |     2/30 (7%)       3/31 (10%)      1/33 (3%)      |     0/33 (0%)       1/42 (2%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         666             675           |      701             731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.464N        P=0.352         P=0.668N       |     P=0.369N        P=0.719N        P=0.495N       |
|INCIDENTAL TUMOR       |     P=0.492N        P=0.350         P=0.686N       |     P=0.404N        P=0.658         P=0.607N       |
|LOGISTIC REGRESSION    |     P=0.483N        P=0.322         P=0.687N       |     P=0.374N        P=0.756N        P=0.501N       |
|COCHRAN-ARMITAGE       |     P=0.500N                                       |     P=0.371N                                       |
|FISHER EXACT           |                     P=0.339         P=0.691N       |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       3/50 (6%)       1/50 (2%)      |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      9.4%            8.9%            2.9%          |      5.3%            0.0%            0.0%          |
|TERMINAL (d)           |     2/30 (7%)       2/31 (6%)       0/33 (0%)      |     1/33 (3%)       0/42 (0%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      708             667             722           |      666             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.215N        P=0.656N        P=0.279N       |     P=0.251N        P=0.209N        P=0.225N       |
|INCIDENTAL TUMOR       |     P=0.248N        P=0.652N        P=0.324N       |     P=0.286N        P=0.342N        P=0.284N       |
|LOGISTIC REGRESSION    |     P=0.224N        P=0.648         P=0.290N       |     P=0.253N        P=0.240N        P=0.238N       |
|COCHRAN-ARMITAGE       |     P=0.237N                                       |     P=0.255N                                       |
|FISHER EXACT           |                     P=0.661N        P=0.309N       |                     P=0.247N        P=0.247N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  13
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       4/50 (8%)       1/50 (2%)      |     4/50 (8%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     12.6%           10.8%            2.9%          |      9.5%            0.0%            0.0%          |
|TERMINAL (d)           |     3/30 (10%)      2/31 (6%)       0/33 (0%)      |     1/33 (3%)       0/42 (0%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      708             437             722           |      541             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.120N        P=0.637N        P=0.158N       |     P=0.082N        P=0.056N        P=0.064N       |
|INCIDENTAL TUMOR       |     P=0.136N        P=0.571N        P=0.187N       |     P=0.080N        P=0.266N        P=0.083N       |
|LOGISTIC REGRESSION    |     P=0.132N        P=0.644N        P=0.165N       |     P=0.060N        P=0.063N        P=0.048N*      |
|COCHRAN-ARMITAGE       |     P=0.133N                                       |     P=0.080N                                       |
|FISHER EXACT           |                     P=0.643N        P=0.181N       |                     P=0.059N        P=0.059N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      3.3%            2.1%            0.0%          |      4.4%            0.0%            0.0%          |
|TERMINAL (d)           |     1/30 (3%)       0/31 (0%)       0/33 (0%)      |     0/33 (0%)       0/42 (0%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         437             ---           |      541             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.363N        P=0.759         P=0.481N       |     P=0.261N        P=0.232N        P=0.244N       |
|INCIDENTAL TUMOR       |     P=0.357N        P=0.660N        P=0.481N       |     P=0.220N        P=0.773N        P=0.262N       |
|LOGISTIC REGRESSION    |     P=0.407N        P=0.717N        P=0.481N       |     P=0.186N        P=0.220N        P=0.173N       |
|COCHRAN-ARMITAGE       |     P=0.371N                                       |     P=0.255N                                       |
|FISHER EXACT           |                     P=0.753N        P=0.500N       |                     P=0.247N        P=0.247N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  14
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    43/50 (86%)     43/50 (86%)     48/50 (96%)     |                                                    |
|ADJUSTED (b)           |     97.7%           97.7%          100.0%          |                                                    |
|TERMINAL (d)           |    29/30 (97%)     30/31 (97%)     33/33 (100%)    |                                                    |
|FIRST INCIDENCE (DAYS) |      558             467             498           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.405         P=0.528N        P=0.459        |                                                    |
|INCIDENTAL TUMOR       |     P=0.064         P=0.474         P=0.051        |                                                    |
|LOGISTIC REGRESSION    |     P=0.047 *       P=0.349         P=0.034 *      |                                                    |
|COCHRAN-ARMITAGE       |     P=0.056                                        |                                                    |
|FISHER EXACT           |                     P=0.613N        P=0.080        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    10/50 (20%)      4/50 (8%)       5/50 (10%)     |     5/50 (10%)      2/50 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |     29.1%           12.9%           13.5%          |     14.6%            4.8%            5.4%          |
|TERMINAL (d)           |     7/30 (23%)      4/31 (13%)      3/33 (9%)      |     4/33 (12%)      2/42 (5%)       2/37 (5%)      |
|FIRST INCIDENCE (DAYS) |      634             729 (T)         436           |      719             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.175N        P=0.070N        P=0.107N       |     P=0.248N        P=0.136N        P=0.177N       |
|INCIDENTAL TUMOR       |     P=0.193N        P=0.087N        P=0.119N       |     P=0.264N        P=0.196N        P=0.207N       |
|LOGISTIC REGRESSION    |     P=0.201N        P=0.082N        P=0.130N       |     P=0.254N        P=0.161N        P=0.189N       |
|COCHRAN-ARMITAGE       |     P=0.213N                                       |     P=0.262N                                       |
|FISHER EXACT           |                     P=0.074N        P=0.131N       |                     P=0.218N        P=0.218N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  15
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      8.2%            0.0%            2.9%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/30 (3%)       0/31 (0%)       0/33 (0%)      |     0/33 (0%)       0/42 (0%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      634             ---             726           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.388N        P=0.127N        P=0.289N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.429N        P=0.180N        P=0.350N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.404N        P=0.120N        P=0.304N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.407N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.121N        P=0.309N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    12/50 (24%)      4/50 (8%)       5/50 (10%)     |     5/50 (10%)      2/50 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |     34.1%           12.9%           13.5%          |     14.6%            4.8%            5.4%          |
|TERMINAL (d)           |     8/30 (27%)      4/31 (13%)      3/33 (9%)      |     4/33 (12%)      2/42 (5%)       2/37 (5%)      |
|FIRST INCIDENCE (DAYS) |      634             729 (T)         436           |      719             731 (T)         731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.092N        P=0.027N*       P=0.044N*      |     P=0.248N        P=0.136N        P=0.177N       |
|INCIDENTAL TUMOR       |     P=0.106N        P=0.033N*       P=0.051N       |     P=0.264N        P=0.196N        P=0.207N       |
|LOGISTIC REGRESSION    |     P=0.107N        P=0.031N*       P=0.054N       |     P=0.254N        P=0.161N        P=0.189N       |
|COCHRAN-ARMITAGE       |     P=0.115N                                       |     P=0.262N                                       |
|FISHER EXACT           |                     P=0.027N*       P=0.054N       |                     P=0.218N        P=0.218N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  16
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |      3.3%            0.0%            3.0%          |      0.0%            4.8%            0.0%          |
|TERMINAL (d)           |     1/30 (3%)       0/31 (0%)       1/33 (3%)      |     0/33 (0%)       2/42 (5%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             729 (T)       |      ---             731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.649         P=0.493N        P=0.741N       |     P=0.493N        P=0.293           (e)          |
|INCIDENTAL TUMOR       |     P=0.649         P=0.493N        P=0.741N       |     P=0.493N        P=0.293           (e)          |
|LOGISTIC REGRESSION    |     P=0.649         P=0.493N        P=0.741N       |     P=0.493N        P=0.293           (e)          |
|COCHRAN-ARMITAGE       |     P=0.629                                        |     P=0.500N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.753N       |                     P=0.247           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       3/50 (6%)       0/50 (0%)      |
|ADJUSTED (b)           |      3.3%            0.0%            3.0%          |      0.0%            7.1%            0.0%          |
|TERMINAL (d)           |     1/30 (3%)       0/31 (0%)       1/33 (3%)      |     0/33 (0%)       3/42 (7%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             729 (T)       |      ---             731 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.649         P=0.493N        P=0.741N       |     P=0.384N        P=0.167           (e)          |
|INCIDENTAL TUMOR       |     P=0.649         P=0.493N        P=0.741N       |     P=0.384N        P=0.167           (e)          |
|LOGISTIC REGRESSION    |     P=0.649         P=0.493N        P=0.741N       |     P=0.384N        P=0.167           (e)          |
|COCHRAN-ARMITAGE       |     P=0.629                                        |     P=0.394N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.753N       |                     P=0.121           (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  17
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)      6/50 (12%)      3/50 (6%)      |
|ADJUSTED (b)           |                                                    |     26.3%           13.5%            8.1%          |
|TERMINAL (d)           |                                                    |     7/33 (21%)      4/42 (10%)      3/37 (8%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      541             666             731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.043N*       P=0.121N        P=0.028N*      |
|INCIDENTAL TUMOR       |                                                    |     P=0.048N*       P=0.296N        P=0.035N*      |
|LOGISTIC REGRESSION    |                                                    |     P=0.044N*       P=0.217N        P=0.037N*      |
|COCHRAN-ARMITAGE       |                                                    |     P=0.044N*                                      |
|FISHER EXACT           |                                                    |                     P=0.207N        P=0.036N*      |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    11/50 (22%)      6/50 (12%)      3/50 (6%)      |
|ADJUSTED (b)           |                                                    |     27.8%           13.5%            8.1%          |
|TERMINAL (d)           |                                                    |     7/33 (21%)      4/42 (10%)      3/37 (8%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      478             666             731 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.030N*       P=0.083N        P=0.018N*      |
|INCIDENTAL TUMOR       |                                                    |     P=0.027N*       P=0.296N        P=0.019N*      |
|LOGISTIC REGRESSION    |                                                    |     P=0.026N*       P=0.161N        P=0.019N*      |
|COCHRAN-ARMITAGE       |                                                    |     P=0.029N*                                      |
|FISHER EXACT           |                                                    |                     P=0.143N        P=0.020N*      |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  18
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    20/50 (40%)     16/50 (32%)     18/50 (36%)     |     7/50 (14%)      8/50 (16%)      7/50 (14%)     |
|ADJUSTED (b)           |     47.5%           38.4%           44.9%          |     18.3%           17.7%           15.3%          |
|TERMINAL (d)           |     9/30 (30%)      7/31 (23%)     12/33 (36%)     |     4/33 (12%)      5/42 (12%)      2/37 (5%)      |
|FIRST INCIDENCE (DAYS) |      512             236             498           |      655             590             453           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.412N        P=0.301N        P=0.349N       |     P=0.533N        P=0.576N        P=0.572N       |
|INCIDENTAL TUMOR       |     P=0.549N        P=0.294N        P=0.423N       |     P=0.552N        P=0.317         P=0.545        |
|LOGISTIC REGRESSION    |     P=0.519N        P=0.230N        P=0.418N       |     P=0.476N        P=0.498         P=0.554N       |
|COCHRAN-ARMITAGE       |     P=0.500N                                       |     P=0.543N                                       |
|FISHER EXACT           |                     P=0.266N        P=0.418N       |                     P=0.500         P=0.613N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.8%            2.6%            6.1%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/30 (3%)       0/31 (0%)       2/33 (6%)      |     0/33 (0%)       0/42 (0%)       0/37 (0%)      |
|FIRST INCIDENCE (DAYS) |      664             674             729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.603         P=0.499N        P=0.668N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.573         P=0.496N        P=0.686N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.592         P=0.504N        P=0.689N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.583                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500N        P=0.691N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  19
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    48/50 (96%)     45/50 (90%)     49/50 (98%)     |    42/50 (84%)     36/50 (72%)     23/50 (46%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     95.4%           78.2%           54.5%          |
|TERMINAL (d)           |    30/30 (100%)    31/31 (100%)    33/33 (100%)    |    31/33 (94%)     32/42 (76%)     18/37 (49%)     |
|FIRST INCIDENCE (DAYS) |      533             467             436           |      541             340             504           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.451N        P=0.327N        P=0.397N       |     P<0.001N**      P=0.004N**      P<0.001N**     |
|INCIDENTAL TUMOR       |     P=0.419         P=0.430N        P=0.691        |     P<0.001N**      P=0.021N*       P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.303         P=0.632N        P=0.392        |     P<0.001N**      P=0.042N*       P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.251                                        |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.218N        P=0.500        |                     P=0.114N        P<0.001N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    25/50 (50%)     25/50 (50%)     28/50 (56%)     |    16/50 (32%)     14/50 (28%)     10/50 (20%)     |
|ADJUSTED (b)           |     57.1%           54.3%           61.9%          |     36.2%           29.6%           22.5%          |
|TERMINAL (d)           |    12/30 (40%)     11/31 (35%)     16/33 (48%)     |     7/33 (21%)      9/42 (21%)      5/37 (14%)     |
|FIRST INCIDENCE (DAYS) |      512             236             498           |      478             578             453           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.445         P=0.562N        P=0.478        |     P=0.135N        P=0.261N        P=0.126N       |
|INCIDENTAL TUMOR       |     P=0.241         P=0.546N        P=0.302        |     P=0.122N        P=0.447         P=0.172N       |
|LOGISTIC REGRESSION    |     P=0.270         P=0.513N        P=0.252        |     P=0.132N        P=0.542         P=0.093N       |
|COCHRAN-ARMITAGE       |     P=0.298                                        |     P=0.116N                                       |
|FISHER EXACT           |                     P=0.579N        P=0.344        |                     P=0.414N        P=0.127N       |
|=================================================================================================================================|
 
         DATE: 09/04/94                     EXPERIMENT: 05029 TEST: 01                                                 PAGE  20
                         STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- DL AMPHETAMINE SULFATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         LOW  M/F        HIGH M/F      |      VEHICLE         LOW  M/F        HIGH M/F      |
|                       |      CONTROL         20PPM           100 PPM       |      CONTROL         20PPM           100 PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    49/50 (98%)     50/50 (100%)    49/50 (98%)     |    48/50 (96%)     42/50 (84%)     30/50 (60%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     98.0%           85.7%           63.6%          |
|TERMINAL (d)           |    30/30 (100%)    31/31 (100%)    33/33 (100%)    |    32/33 (97%)     35/42 (83%)     20/37 (54%)     |
|FIRST INCIDENCE (DAYS) |      512             236             436           |      478             340             453           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.287N        P=0.531         P=0.336N       |     P<0.001N**      P=0.006N**      P<0.001N**     |
|INCIDENTAL TUMOR       |     P=0.404N        P=0.500         P=0.581N       |     P<0.001N**      P=0.048N*       P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.430N        P=0.266         P=0.581N       |     P<0.001N**      P=0.045N*       P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.629N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.500         P=0.753N       |                     P=0.046N*       P<0.001N**     |
|=================================================================================================================================|
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
 
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).

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