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TDMS Study 05150-01 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                            METHLYPHENIDATE HYDROCHLORIDE                            DATE: 05/20/95       
EXPERIMENT: 05150 TEST: 01                                                                                     TIME: 09:27:31       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01ES65132                                ROUTE: DOSED FEED                                              NTP C#: 266          
PATHOLOGIST: A. RUSSFIELD                                                                                      CAS: 298-59-9        
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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: Mason                                            METHLYPHENIDATE HYDROCHLORIDE                            DATE: 05/20/95       
EXPERIMENT: 05150 TEST: 01                                                                                     TIME: 09:27:31       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES65132                                ROUTE: DOSED FEED                                              NTP C#: 266          
PATHOLOGIST: A. RUSSFIELD                                                                                      CAS: 298-59-9        


                                                    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 Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Clitoral/Preputial Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                            METHLYPHENIDATE HYDROCHLORIDE                            DATE: 05/20/95       
EXPERIMENT: 05150 TEST: 01                                                                                     TIME: 09:27:31       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES65132                                ROUTE: DOSED FEED                                              NTP C#: 266          
PATHOLOGIST: A. RUSSFIELD                                                                                      CAS: 298-59-9        


                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                 IN THE ANALYSIS OF THE STUDY OF METHLYPHENIDATE HYDROCHLORIDE
              ====================================================================================================
                                                           MALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Adrenal Medulla               Pheochromocytoma Benign
                                            Pheochromocytoma: Benign, Complex, Malignant, NOS
              Testes                        Adenoma
              All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated
              ====================================================================================================
                                                           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
              All Organs                    Benign Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   1
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 17/69 (25%)   6/68 (9%)    5/69 (7%)   11/69 (16%) |  3/70 (4%)    3/69 (4%)    3/70 (4%)    3/70 (4%)  |
|ADJUSTED (b)           |  50.8%        17.9%        13.8%        31.6%      |   9.7%         9.7%         7.6%         7.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           | 12/28 (43%)   5/32 (16%)   4/34 (12%)  10/33 (30%) |  3/31 (10%)   3/31 (10%)   2/36 (6%)    3/39 (8%)  |
|FIRST INCIDENCE (DAYS) |   639          676          653          462 (I)   |   737 (T)      737 (T)      546          737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.191N     P=0.004N**   P=0.001N**   P=0.059N   |  P=0.449N     P=0.665      P=0.607N     P=0.553N   |
|INCIDENTAL TUMOR       |  P=0.218N     P=0.006N**   P=0.001N**   P=0.084N   |  P=0.423N     P=0.665      P=0.505N     P=0.553N   |
|LOGISTIC REGRESSION    |  P=0.235N     P=0.005N**   P=0.001N**   P=0.096N   |  P=0.539N     P=0.665      P=0.651N     P=0.553N   |
|COCHRAN-ARMITAGE       |  P=0.285N                                          |  P=0.570N                                          |
|FISHER EXACT           |               P=0.011N*    P=0.005N**   P=0.145N   |               P=0.653      P=0.660N     P=0.660N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/69 (1%)    1/68 (1%)    1/69 (1%)    0/69 (0%)  |  0/70 (0%)    1/69 (1%)    2/70 (3%)    0/70 (0%)  |
|ADJUSTED (b)           |   3.6%         3.1%         2.9%         0.0%      |   0.0%         3.2%         5.6%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    1/32 (3%)    1/34 (3%)    0/33 (0%)  |  0/31 (0%)    1/31 (3%)    2/36 (6%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      ---       |   ---          737 (T)      737 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.273N     P=0.732N     P=0.718N     P=0.467N   |  P=0.520N     P=0.500      P=0.272        (e)      |
|INCIDENTAL TUMOR       |  P=0.273N     P=0.732N     P=0.718N     P=0.467N   |  P=0.520N     P=0.500      P=0.272        (e)      |
|LOGISTIC REGRESSION    |  P=0.273N     P=0.732N     P=0.718N     P=0.467N   |  P=0.520N     P=0.500      P=0.272        (e)      |
|COCHRAN-ARMITAGE       |  P=0.301N                                          |  P=0.586N                                          |
|FISHER EXACT           |               P=0.748      P=0.752N     P=0.500N   |               P=0.496      P=0.248        (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   2
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 18/69 (26%)   7/68 (10%)   5/69 (7%)   11/69 (16%) |  3/70 (4%)    4/69 (6%)    5/70 (7%)    3/70 (4%)  |
|ADJUSTED (b)           |  53.9%        20.9%        13.8%        31.6%      |   9.7%        12.9%        13.0%         7.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           | 13/28 (46%)   6/32 (19%)   4/34 (12%)  10/33 (30%) |  3/31 (10%)   4/31 (13%)   4/36 (11%)   3/39 (8%)  |
|FIRST INCIDENCE (DAYS) |   639          676          653          462 (I)   |   737 (T)      737 (T)      546          737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.117N     P=0.004N**   P<0.001N**   P=0.037N*  |  P=0.396N     P=0.500      P=0.427      P=0.553N   |
|INCIDENTAL TUMOR       |  P=0.135N     P=0.007N**   P<0.001N**   P=0.053N   |  P=0.374N     P=0.500      P=0.518      P=0.553N   |
|LOGISTIC REGRESSION    |  P=0.148N     P=0.006N**   P<0.001N**   P=0.062N   |  P=0.495N     P=0.500      P=0.375      P=0.553N   |
|COCHRAN-ARMITAGE       |  P=0.196N                                          |  P=0.536N                                          |
|FISHER EXACT           |               P=0.014N*    P=0.003N**   P=0.105N   |               P=0.492      P=0.359      P=0.660N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    2/67 (3%)    2/70 (3%)    1/70 (1%)  |  1/65 (2%)    1/68 (1%)    1/69 (1%)    0/69 (0%)  |
|ADJUSTED (b)           |   7.1%         4.8%         5.9%         2.9%      |   3.7%         2.5%         2.2%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  2/28 (7%)    1/33 (3%)    2/34 (6%)    1/34 (3%)  |  1/27 (4%)    0/30 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      462 (I)      729 (T)      729 (T)   |   737 (T)      699          567          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.321N     P=0.649N     P=0.624N     P=0.432N   |  P=0.271N     P=0.727N     P=0.731N     P=0.427N   |
|INCIDENTAL TUMOR       |  P=0.321N     P=0.649N     P=0.624N     P=0.432N   |  P=0.378N     P=0.749N     P=0.723      P=0.427N   |
|LOGISTIC REGRESSION    |  P=0.348N     P=0.682      P=0.624N     P=0.432N   |  P=0.285N     P=0.732N     P=0.744N     P=0.427N   |
|COCHRAN-ARMITAGE       |  P=0.359N                                          |  P=0.292N                                          |
|FISHER EXACT           |               P=0.674      P=0.690N     P=0.500N   |               P=0.740N     P=0.737N     P=0.485N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   3
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/67 (3%)    4/70 (6%)    2/70 (3%)  |  0/65 (0%)    0/68 (0%)    0/69 (0%)    0/69 (0%)  |
|ADJUSTED (b)           |   0.0%         6.1%        11.8%         5.3%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    2/33 (6%)    4/34 (12%)   0/34 (0%)  |  0/27 (0%)    0/30 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      729 (T)      675       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.297      P=0.275      P=0.089      P=0.280    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.283      P=0.275      P=0.089      P=0.178    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.277      P=0.275      P=0.089      P=0.246    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.255                                           |    (e)                                             |
|FISHER EXACT           |               P=0.237      P=0.060      P=0.248    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    4/67 (6%)    6/70 (9%)    3/70 (4%)  |  1/65 (2%)    1/68 (1%)    1/69 (1%)    0/69 (0%)  |
|ADJUSTED (b)           |   7.1%        10.7%        17.6%         8.1%      |   3.7%         2.5%         2.2%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  2/28 (7%)    3/33 (9%)    6/34 (18%)   1/34 (3%)  |  1/27 (4%)    0/30 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      462 (I)      729 (T)      675       |   737 (T)      699          567          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.539      P=0.402      P=0.200      P=0.584    |  P=0.271N     P=0.727N     P=0.731N     P=0.427N   |
|INCIDENTAL TUMOR       |  P=0.528      P=0.402      P=0.200      P=0.507    |  P=0.378N     P=0.749N     P=0.723      P=0.427N   |
|LOGISTIC REGRESSION    |  P=0.498      P=0.327      P=0.200      P=0.537    |  P=0.285N     P=0.732N     P=0.744N     P=0.427N   |
|COCHRAN-ARMITAGE       |  P=0.473                                           |  P=0.292N                                          |
|FISHER EXACT           |               P=0.320      P=0.137      P=0.500    |               P=0.740N     P=0.737N     P=0.485N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   4
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/69 (1%)    0/70 (0%)    1/70 (1%)    2/69 (3%)  |  0/70 (0%)    2/69 (3%)    1/70 (1%)    2/70 (3%)  |
|ADJUSTED (b)           |   3.6%         0.0%         1.8%         5.6%      |   0.0%         6.5%         2.8%         5.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/33 (0%)    0/34 (0%)    1/34 (3%)  |  0/31 (0%)    2/31 (6%)    1/36 (3%)    2/39 (5%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          462 (I)      686       |   ---          737 (T)      737 (T)      737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.223      P=0.467N     P=0.739N     P=0.555    |  P=0.386      P=0.238      P=0.530      P=0.290    |
|INCIDENTAL TUMOR       |  P=0.211      P=0.467N     P=0.739N     P=0.516    |  P=0.386      P=0.238      P=0.530      P=0.290    |
|LOGISTIC REGRESSION    |  P=0.203      P=0.467N     P=0.759N     P=0.526    |  P=0.386      P=0.238      P=0.530      P=0.290    |
|COCHRAN-ARMITAGE       |  P=0.201                                           |  P=0.305                                           |
|FISHER EXACT           |               P=0.496N     P=0.748N     P=0.500    |               P=0.245      P=0.500      P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/69 (0%)    2/70 (3%)    0/70 (0%)    2/69 (3%)  |  0/70 (0%)    0/69 (0%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         5.2%         0.0%         5.9%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    1/33 (3%)    0/34 (0%)    2/34 (6%)  |  0/31 (0%)    0/31 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          596          ---          729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.357      P=0.263        (e)        P=0.282    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.284      P=0.192        (e)        P=0.282    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.334      P=0.242        (e)        P=0.282    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.325                                           |    (e)                                             |
|FISHER EXACT           |               P=0.252        (e)        P=0.248    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   5
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/69 (1%)    2/70 (3%)    1/70 (1%)    4/69 (6%)  |  0/70 (0%)    2/69 (3%)    1/70 (1%)    2/70 (3%)  |
|ADJUSTED (b)           |   3.6%         5.2%         1.8%        11.4%      |   0.0%         6.5%         2.8%         5.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    1/33 (3%)    0/34 (0%)    3/34 (9%)  |  0/31 (0%)    2/31 (6%)    1/36 (3%)    2/39 (5%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      596          462 (I)      686       |   ---          737 (T)      737 (T)      737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.151      P=0.543      P=0.739N     P=0.236    |  P=0.386      P=0.238      P=0.530      P=0.290    |
|INCIDENTAL TUMOR       |  P=0.113      P=0.471      P=0.739N     P=0.213    |  P=0.386      P=0.238      P=0.530      P=0.290    |
|LOGISTIC REGRESSION    |  P=0.129      P=0.510      P=0.759N     P=0.207    |  P=0.386      P=0.238      P=0.530      P=0.290    |
|COCHRAN-ARMITAGE       |  P=0.126                                           |  P=0.305                                           |
|FISHER EXACT           |               P=0.505      P=0.748N     P=0.183    |               P=0.245      P=0.500      P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/69 (0%)    1/70 (1%)    0/70 (0%)    0/67 (0%)  |  0/70 (0%)    1/69 (1%)    0/68 (0%)    2/69 (3%)  |
|ADJUSTED (b)           |   0.0%         3.0%         0.0%         0.0%      |   0.0%         1.7%         0.0%         5.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    1/33 (3%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    0/32 (0%)    0/36 (0%)    2/39 (5%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   ---          463 (I)      ---          737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.428N     P=0.533        (e)          (e)      |  P=0.200      P=0.500        (e)        P=0.290    |
|INCIDENTAL TUMOR       |  P=0.428N     P=0.533        (e)          (e)      |  P=0.200      P=0.500        (e)        P=0.290    |
|LOGISTIC REGRESSION    |  P=0.428N     P=0.533        (e)          (e)      |  P=0.169      P=0.488        (e)        P=0.290    |
|COCHRAN-ARMITAGE       |  P=0.454N                                          |  P=0.167                                           |
|FISHER EXACT           |               P=0.504        (e)          (e)      |               P=0.496        (e)        P=0.245    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   6
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    1/70 (1%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         5.7%         0.0%         0.0%      |   0.0%         3.1%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    1/33 (3%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    1/32 (3%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          676          ---          ---       |   ---          737 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.243N     P=0.264        (e)          (e)      |  P=0.415N     P=0.506        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.260N     P=0.229        (e)          (e)      |  P=0.415N     P=0.506        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.256N     P=0.247        (e)          (e)      |  P=0.415N     P=0.506        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.264N                                          |  P=0.449N                                          |
|FISHER EXACT           |               P=0.248        (e)          (e)      |               P=0.500        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/70 (1%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    3/70 (4%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   5.3%         3.0%         0.0%         0.0%      |   0.0%         7.8%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    1/33 (3%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    2/32 (6%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   462 (I)      729 (T)      ---          ---       |   ---          463 (I)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.095N     P=0.462N     P=0.218N     P=0.218N   |  P=0.147N     P=0.127        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.095N     P=0.462N     P=0.218N     P=0.218N   |  P=0.147N     P=0.127        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.104N     P=0.499N     P=0.238N     P=0.239N   |  P=0.168N     P=0.124        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.105N                                          |  P=0.169N                                          |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |               P=0.122        (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   7
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |  1/70 (1%)    4/70 (6%)    1/70 (1%)    1/70 (1%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   3.2%        11.3%         2.8%         2.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/33 (0%)    0/34 (0%)    0/34 (0%)  |  1/31 (3%)    2/32 (6%)    1/36 (3%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   737 (T)      699          737 (T)      619       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.212N     P=0.203      P=0.728N     P=0.733N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.316N     P=0.177      P=0.728N     P=0.735N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.249N     P=0.204      P=0.728N     P=0.755N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.264N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.183      P=0.752N     P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |  1/70 (1%)    4/70 (6%)    2/70 (3%)    1/70 (1%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   3.2%        11.3%         5.6%         2.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/33 (0%)    0/34 (0%)    0/34 (0%)  |  1/31 (3%)    2/32 (6%)    2/36 (6%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   737 (T)      699          737 (T)      619       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.244N     P=0.203      P=0.552      P=0.733N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.350N     P=0.177      P=0.552      P=0.735N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.290N     P=0.204      P=0.552      P=0.755N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.308N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.183      P=0.500      P=0.752N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   8
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    2/70 (3%)    1/70 (1%)    2/70 (3%)  | 15/70 (21%)  13/70 (19%)   6/70 (9%)    5/70 (7%)  |
|ADJUSTED (b)           |   3.6%         6.1%         2.9%         5.9%      |  45.3%        38.0%        15.9%        11.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    2/33 (6%)    1/34 (3%)    2/34 (6%)  | 13/31 (42%)  11/32 (34%)   5/36 (14%)   3/39 (8%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   680          720          638          559       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P<0.001N**   P=0.361N     P=0.010N**   P=0.003N** |
|INCIDENTAL TUMOR       |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P=0.001N**   P=0.389N     P=0.017N*    P=0.006N** |
|LOGISTIC REGRESSION    |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P=0.002N**   P=0.280N     P=0.013N*    P=0.007N** |
|COCHRAN-ARMITAGE       |  P=0.479                                           |  P=0.004N**                                        |
|FISHER EXACT           |               P=0.500      P=0.752N     P=0.500    |               P=0.416N     P=0.028N*    P=0.014N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    2/70 (3%)    1/70 (1%)    2/70 (3%)  | 15/70 (21%)  13/70 (19%)   7/70 (10%)   5/70 (7%)  |
|ADJUSTED (b)           |   3.6%         6.1%         2.9%         5.9%      |  45.3%        38.0%        18.6%        11.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    2/33 (6%)    1/34 (3%)    2/34 (6%)  | 13/31 (42%)  11/32 (34%)   6/36 (17%)   3/39 (8%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   680          720          638          559       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P<0.001N**   P=0.361N     P=0.019N*    P=0.003N** |
|INCIDENTAL TUMOR       |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P=0.002N**   P=0.389N     P=0.031N*    P=0.006N** |
|LOGISTIC REGRESSION    |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P=0.002N**   P=0.280N     P=0.025N*    P=0.007N** |
|COCHRAN-ARMITAGE       |  P=0.479                                           |  P=0.005N**                                        |
|FISHER EXACT           |               P=0.500      P=0.752N     P=0.500    |               P=0.416N     P=0.051N     P=0.014N*  |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE   9
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    2/70 (3%)    1/70 (1%)    2/70 (3%)  | 16/70 (23%)  17/70 (24%)   8/70 (11%)   5/70 (7%)  |
|ADJUSTED (b)           |   3.6%         6.1%         2.9%         5.9%      |  48.3%        46.9%        21.3%        11.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    2/33 (6%)    1/34 (3%)    2/34 (6%)  | 14/31 (45%)  13/32 (41%)   7/36 (19%)   3/39 (8%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   680          699          638          559       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P<0.001N**   P=0.561      P=0.019N*    P=0.002N** |
|INCIDENTAL TUMOR       |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P<0.001N**   P=0.517      P=0.032N*    P=0.003N** |
|LOGISTIC REGRESSION    |  P=0.532      P=0.558      P=0.718N     P=0.568    |  P<0.001N**   P=0.527N     P=0.026N*    P=0.004N** |
|COCHRAN-ARMITAGE       |  P=0.479                                           |  P=0.001N**                                        |
|FISHER EXACT           |               P=0.500      P=0.752N     P=0.500    |               P=0.500      P=0.058N     P=0.008N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/69 (0%)    0/70 (0%)    2/69 (3%)    1/69 (1%)  |  0/70 (0%)    0/69 (0%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         5.9%         2.9%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/33 (0%)    2/34 (6%)    1/34 (3%)  |  0/31 (0%)    0/31 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          729 (T)      729 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.236        (e)        P=0.282      P=0.539    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.236        (e)        P=0.282      P=0.539    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.236        (e)        P=0.282      P=0.539    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.207                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.248      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  10
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 12/68 (18%)  11/69 (16%)   7/68 (10%)  11/70 (16%) | 28/70 (40%)  33/69 (48%)  22/69 (32%)  25/67 (37%) |
|ADJUSTED (b)           |  35.5%        27.0%        21.2%        29.6%      |  65.6%        75.8%        52.6%        59.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   1/10 (10%)   0/10 (0%)    1/10 (10%) |  2/10 (20%)   1/10 (10%)   2/10 (20%)   0/9 (0%)   |
|TERMINAL (d)           |  8/28 (29%)   6/33 (18%)   7/33 (21%)   9/34 (26%) | 17/31 (55%)  21/31 (68%)  17/36 (47%)  21/38 (55%) |
|FIRST INCIDENCE (DAYS) |   462 (I)      409          729 (T)      462 (I)   |   463 (I)      450          463 (I)      404       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.298N     P=0.388N     P=0.084N     P=0.336N   |  P=0.022N*    P=0.301      P=0.085N     P=0.136N   |
|INCIDENTAL TUMOR       |  P=0.350N     P=0.471N     P=0.106N     P=0.411N   |  P=0.115N     P=0.222      P=0.243N     P=0.384N   |
|LOGISTIC REGRESSION    |  P=0.362N     P=0.474N     P=0.108N     P=0.439N   |  P=0.096N     P=0.240      P=0.154N     P=0.325N   |
|COCHRAN-ARMITAGE       |  P=0.385N                                          |  P=0.170N                                          |
|FISHER EXACT           |               P=0.485N     P=0.161N     P=0.469N   |               P=0.224      P=0.206N     P=0.442N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/68 (19%)  11/69 (16%)   7/68 (10%)  11/70 (16%) | 28/70 (40%)  33/69 (48%)  23/69 (33%)  25/67 (37%) |
|ADJUSTED (b)           |  37.0%        27.0%        21.2%        29.6%      |  65.6%        75.8%        55.1%        59.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|INTERIM SACRIFICE 2 (c)|  1/10 (10%)   1/10 (10%)   0/10 (0%)    1/10 (10%) |  2/10 (20%)   1/10 (10%)   2/10 (20%)   0/9 (0%)   |
|TERMINAL (d)           |  8/28 (29%)   6/33 (18%)   7/33 (21%)   9/34 (26%) | 17/31 (55%)  21/31 (68%)  18/36 (50%)  21/38 (55%) |
|FIRST INCIDENCE (DAYS) |   462 (I)      409          729 (T)      462 (I)   |   463 (I)      450          463 (I)      404       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.244N     P=0.310N     P=0.056N     P=0.261N   |  P=0.023N*    P=0.301      P=0.114N     P=0.136N   |
|INCIDENTAL TUMOR       |  P=0.310N     P=0.416N     P=0.088N     P=0.368N   |  P=0.120N     P=0.222      P=0.303N     P=0.384N   |
|LOGISTIC REGRESSION    |  P=0.301N     P=0.385N     P=0.075N     P=0.354N   |  P=0.101N     P=0.240      P=0.204N     P=0.325N   |
|COCHRAN-ARMITAGE       |  P=0.322N                                          |  P=0.179N                                          |
|FISHER EXACT           |               P=0.396N     P=0.113N     P=0.381N   |               P=0.224      P=0.261N     P=0.442N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  11
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |  1/70 (1%)    1/70 (1%)    0/70 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   0.0%         6.1%         0.0%         0.0%      |   2.9%         3.1%         0.0%         2.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    2/33 (6%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    1/32 (3%)    0/36 (0%)    1/39 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   684          737 (T)      ---          737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.240N     P=0.275        (e)          (e)      |  P=0.537N     P=0.736N     P=0.473N     P=0.716N   |
|INCIDENTAL TUMOR       |  P=0.240N     P=0.275        (e)          (e)      |  P=0.646N     P=0.755      P=0.654N     P=0.673    |
|LOGISTIC REGRESSION    |  P=0.240N     P=0.275        (e)          (e)      |  P=0.574N     P=0.751N     P=0.497N     P=0.749N   |
|COCHRAN-ARMITAGE       |  P=0.264N                                          |  P=0.588N                                          |
|FISHER EXACT           |               P=0.248        (e)          (e)      |               P=0.752N     P=0.500N     P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma, Basosquamous Tumor Benign, or Trichoepithelioma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |  2/70 (3%)    1/70 (1%)    0/70 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   0.0%         6.1%         0.0%         0.0%      |   4.6%         3.1%         0.0%         2.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    2/33 (6%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    1/32 (3%)    0/36 (0%)    1/39 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   450          737 (T)      ---          737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.240N     P=0.275        (e)          (e)      |  P=0.338N     P=0.473N     P=0.227N     P=0.457N   |
|INCIDENTAL TUMOR       |  P=0.240N     P=0.275        (e)          (e)      |  P=0.375N     P=0.387N     P=0.158N     P=0.478N   |
|LOGISTIC REGRESSION    |  P=0.240N     P=0.275        (e)          (e)      |  P=0.372N     P=0.498N     P=0.238N     P=0.498N   |
|COCHRAN-ARMITAGE       |  P=0.264N                                          |  P=0.375N                                          |
|FISHER EXACT           |               P=0.248        (e)          (e)      |               P=0.500N     P=0.248N     P=0.500N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  12
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous Tumor (benign,                                                       |
|     malignant or NOS), or Trichoepithelioma                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |  2/70 (3%)    1/70 (1%)    0/70 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   0.0%         6.1%         0.0%         0.0%      |   4.6%         3.1%         0.0%         2.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    2/33 (6%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    1/32 (3%)    0/36 (0%)    1/39 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          729 (T)      ---          ---       |   450          737 (T)      ---          737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.240N     P=0.275        (e)          (e)      |  P=0.338N     P=0.473N     P=0.227N     P=0.457N   |
|INCIDENTAL TUMOR       |  P=0.240N     P=0.275        (e)          (e)      |  P=0.375N     P=0.387N     P=0.158N     P=0.478N   |
|LOGISTIC REGRESSION    |  P=0.240N     P=0.275        (e)          (e)      |  P=0.372N     P=0.498N     P=0.238N     P=0.498N   |
|COCHRAN-ARMITAGE       |  P=0.264N                                          |  P=0.375N                                          |
|FISHER EXACT           |               P=0.248        (e)          (e)      |               P=0.500N     P=0.248N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal                                                       |
|     Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepithelioma                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    3/70 (4%)    4/70 (6%)    1/70 (1%)  |  2/70 (3%)    1/70 (1%)    0/70 (0%)    2/70 (3%)  |
|ADJUSTED (b)           |   7.1%         9.1%        10.9%         2.9%      |   4.6%         3.1%         0.0%         4.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |
|TERMINAL (d)           |  2/28 (7%)    3/33 (9%)    3/34 (9%)    1/34 (3%)  |  0/31 (0%)    1/32 (3%)    0/36 (0%)    1/39 (3%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      653          729 (T)   |   450          737 (T)      ---          463 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.294N     P=0.576      P=0.426      P=0.432N   |  P=0.603      P=0.473N     P=0.227N     P=0.658N   |
|INCIDENTAL TUMOR       |  P=0.304N     P=0.575      P=0.414      P=0.432N   |  P=0.565      P=0.387N     P=0.158N     P=0.689N   |
|LOGISTIC REGRESSION    |  P=0.318N     P=0.575      P=0.393      P=0.432N   |  P=0.569      P=0.498N     P=0.238N     P=0.692    |
|COCHRAN-ARMITAGE       |  P=0.356N                                          |  P=0.568                                           |
|FISHER EXACT           |               P=0.500      P=0.340      P=0.500N   |               P=0.500N     P=0.248N     P=0.690N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  13
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    3/70 (4%)    1/70 (1%)    3/70 (4%)  |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   2.1%         9.1%         2.9%         8.1%      |   0.0%         6.3%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    3/33 (9%)    1/34 (3%)    2/34 (6%)  |  0/31 (0%)    2/32 (6%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   524          729 (T)      729 (T)      639       |   ---          737 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.420      P=0.349      P=0.739N     P=0.346    |  P=0.227N     P=0.245        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.365      P=0.351      P=0.739N     P=0.248    |  P=0.227N     P=0.245        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.385      P=0.312      P=0.759N     P=0.308    |  P=0.227N     P=0.245        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.375                                           |  P=0.264N                                          |
|FISHER EXACT           |               P=0.310      P=0.752N     P=0.310    |               P=0.248        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    4/70 (6%)    2/70 (3%)    3/70 (4%)  |  0/70 (0%)    4/70 (6%)    1/70 (1%)    0/70 (0%)  |
|ADJUSTED (b)           |   5.6%        11.3%         5.0%         8.1%      |   0.0%        11.3%         2.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    3/33 (9%)    1/34 (3%)    2/34 (6%)  |  0/31 (0%)    3/32 (9%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   524          623          542          639       |   ---          579          588          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.531N     P=0.390      P=0.656N     P=0.555    |  P=0.140N     P=0.069      P=0.496        (e)      |
|INCIDENTAL TUMOR       |  P=0.531      P=0.344      P=0.666N     P=0.461    |  P=0.133N     P=0.058      P=0.443        (e)      |
|LOGISTIC REGRESSION    |  P=0.571N     P=0.346      P=0.688N     P=0.506    |  P=0.162N     P=0.068      P=0.500        (e)      |
|COCHRAN-ARMITAGE       |  P=0.577N                                          |  P=0.165N                                          |
|FISHER EXACT           |               P=0.340      P=0.690N     P=0.500    |               P=0.060      P=0.500        (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  14
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/70 (1%)    1/70 (1%)    0/70 (0%)  |  0/70 (0%)    2/70 (3%)    1/70 (1%)    0/70 (0%)  |
|ADJUSTED (b)           |   3.6%         2.4%         2.1%         0.0%      |   0.0%         5.2%         2.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/33 (0%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    1/32 (3%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      623          542          ---       |   ---          579          588          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.292N     P=0.739N     P=0.737N     P=0.461N   |  P=0.338N     P=0.248      P=0.496        (e)      |
|INCIDENTAL TUMOR       |  P=0.369N     P=0.718      P=0.739N     P=0.461N   |  P=0.324N     P=0.212      P=0.443        (e)      |
|LOGISTIC REGRESSION    |  P=0.302N     P=0.758N     P=0.758N     P=0.461N   |  P=0.416N     P=0.242      P=0.500        (e)      |
|COCHRAN-ARMITAGE       |  P=0.303N                                          |  P=0.356N                                          |
|FISHER EXACT           |               P=0.752N     P=0.752N     P=0.500N   |               P=0.248      P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/70 (1%)    4/70 (6%)    1/70 (1%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   3.6%         3.0%        10.9%         2.9%      |   0.0%         0.0%         0.0%         1.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |
|TERMINAL (d)           |  1/28 (4%)    1/33 (3%)    3/34 (9%)    1/34 (3%)  |  0/31 (0%)    0/32 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      653          729 (T)   |   ---          ---          ---          463 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.536      P=0.725N     P=0.240      P=0.718N   |  P=0.187        (e)          (e)        P=0.500    |
|INCIDENTAL TUMOR       |  P=0.522      P=0.725N     P=0.230      P=0.718N   |  P=0.187        (e)          (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.508      P=0.725N     P=0.214      P=0.718N   |  P=0.184        (e)          (e)        P=0.493    |
|COCHRAN-ARMITAGE       |  P=0.481                                           |  P=0.187                                           |
|FISHER EXACT           |               P=0.752N     P=0.183      P=0.752N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  15
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/70 (1%)    4/70 (6%)    1/70 (1%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   7.1%         3.0%        10.9%         2.9%      |   0.0%         0.0%         0.0%         1.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |
|TERMINAL (d)           |  2/28 (7%)    1/33 (3%)    3/34 (9%)    1/34 (3%)  |  0/31 (0%)    0/32 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      653          729 (T)   |   ---          ---          ---          463 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.495N     P=0.442N     P=0.426      P=0.432N   |  P=0.187        (e)          (e)        P=0.500    |
|INCIDENTAL TUMOR       |  P=0.508N     P=0.442N     P=0.414      P=0.432N   |  P=0.187        (e)          (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.524N     P=0.442N     P=0.393      P=0.432N   |  P=0.184        (e)          (e)        P=0.493    |
|COCHRAN-ARMITAGE       |  P=0.554N                                          |  P=0.187                                           |
|FISHER EXACT           |               P=0.500N     P=0.340      P=0.500N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/70 (1%)    4/70 (6%)    1/70 (1%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   7.1%         3.0%        10.9%         2.9%      |   0.0%         0.0%         0.0%         1.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |
|TERMINAL (d)           |  2/28 (7%)    1/33 (3%)    3/34 (9%)    1/34 (3%)  |  0/31 (0%)    0/32 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      653          729 (T)   |   ---          ---          ---          463 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.495N     P=0.442N     P=0.426      P=0.432N   |  P=0.187        (e)          (e)        P=0.500    |
|INCIDENTAL TUMOR       |  P=0.508N     P=0.442N     P=0.414      P=0.432N   |  P=0.187        (e)          (e)        P=0.500    |
|LOGISTIC REGRESSION    |  P=0.524N     P=0.442N     P=0.393      P=0.432N   |  P=0.184        (e)          (e)        P=0.493    |
|COCHRAN-ARMITAGE       |  P=0.554N                                          |  P=0.187                                           |
|FISHER EXACT           |               P=0.500N     P=0.340      P=0.500N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  16
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    0/69 (0%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   5.9%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/33 (0%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    0/31 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   612          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.151N     P=0.222N     P=0.211N     P=0.218N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.214N     P=0.282N     P=0.326N     P=0.326N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.158N     P=0.234N     P=0.227N     P=0.235N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.161N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 55/70 (79%)  56/69 (81%)  55/70 (79%)  57/70 (81%) |                                                    |
|ADJUSTED (b)           |  98.2%       100.0%       100.0%       100.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |                                                    |
|INTERIM SACRIFICE 2 (c)|  9/10 (90%)  10/10 (100%)  8/10 (80%)  10/10 (100%)|                                                    |
|TERMINAL (d)           | 27/28 (96%)  33/33 (100%) 34/34 (100%) 34/34 (100%)|                                                    |
|FIRST INCIDENCE (DAYS) |   459          429          462 (I)      275 (I)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.251N     P=0.262N     P=0.125N     P=0.251N   |                                                    |
|INCIDENTAL TUMOR       |  P=0.165      P=0.199      P=0.595N     P=0.126    |                                                    |
|LOGISTIC REGRESSION    |  P=0.037 *    P=0.594N     P=0.542      P=0.110    |                                                    |
|COCHRAN-ARMITAGE       |  P=0.438                                           |                                                    |
|FISHER EXACT           |               P=0.433      P=0.581N     P=0.416    |                                                    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  17
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/70 (6%)    5/69 (7%)    6/70 (9%)    9/69 (13%) |  4/70 (6%)    8/70 (11%)   7/70 (10%)   4/70 (6%)  |
|ADJUSTED (b)           |  14.3%        13.1%        16.9%        23.9%      |   9.3%        22.5%        18.9%        10.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    1/10 (10%) |  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  4/28 (14%)   3/32 (9%)    5/34 (15%)   7/34 (21%) |  1/31 (3%)    6/32 (19%)   6/36 (17%)   4/39 (10%) |
|FIRST INCIDENCE (DAYS) |   729 (T)      462 (I)      681          462 (I)   |   463 (I)      660          730          737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.115      P=0.566      P=0.494      P=0.193    |  P=0.236N     P=0.210      P=0.330      P=0.560N   |
|INCIDENTAL TUMOR       |  P=0.080      P=0.525      P=0.483      P=0.149    |  P=0.401N     P=0.177      P=0.203      P=0.577    |
|LOGISTIC REGRESSION    |  P=0.082      P=0.501      P=0.473      P=0.132    |  P=0.330N     P=0.197      P=0.273      P=0.625N   |
|COCHRAN-ARMITAGE       |  P=0.073                                           |  P=0.360N                                          |
|FISHER EXACT           |               P=0.491      P=0.372      P=0.116    |               P=0.183      P=0.266      P=0.641N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/69 (0%)    2/70 (3%)    1/69 (1%)  |  1/70 (1%)    2/70 (3%)    0/70 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   3.6%         0.0%         5.9%         2.9%      |   3.2%         6.3%         0.0%         2.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/32 (0%)    2/34 (6%)    1/34 (3%)  |  1/31 (3%)    2/32 (6%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      ---          729 (T)      729 (T)   |   737 (T)      737 (T)      ---          676       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.471      P=0.473N     P=0.568      P=0.718N   |  P=0.368N     P=0.511      P=0.470N     P=0.720N   |
|INCIDENTAL TUMOR       |  P=0.471      P=0.473N     P=0.568      P=0.718N   |  P=0.451N     P=0.511      P=0.470N     P=0.673    |
|LOGISTIC REGRESSION    |  P=0.471      P=0.473N     P=0.569      P=0.718N   |  P=0.407N     P=0.511      P=0.470N     P=0.750N   |
|COCHRAN-ARMITAGE       |  P=0.422                                           |  P=0.424N                                          |
|FISHER EXACT           |               P=0.504N     P=0.500      P=0.748    |               P=0.500      P=0.500N     P=0.752N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  18
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/70 (7%)    5/69 (7%)    7/70 (10%)  10/69 (14%) |  5/70 (7%)   10/70 (14%)   7/70 (10%)   5/70 (7%)  |
|ADJUSTED (b)           |  17.9%        13.1%        19.8%        26.7%      |  12.3%        28.5%        18.9%        12.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   0/10 (0%)    1/10 (10%) |  1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  5/28 (18%)   3/32 (9%)    6/34 (18%)   8/34 (24%) |  2/31 (6%)    8/32 (25%)   6/36 (17%)   4/39 (10%) |
|FIRST INCIDENCE (DAYS) |   729 (T)      462 (I)      681          462 (I)   |   463 (I)      660          730          676       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.103      P=0.560N     P=0.519      P=0.222    |  P=0.175N     P=0.160      P=0.460      P=0.531N   |
|INCIDENTAL TUMOR       |  P=0.072      P=0.599N     P=0.508      P=0.176    |  P=0.337N     P=0.134      P=0.320      P=0.513    |
|LOGISTIC REGRESSION    |  P=0.071      P=0.628N     P=0.499      P=0.151    |  P=0.262N     P=0.152      P=0.394      P=0.607N   |
|COCHRAN-ARMITAGE       |  P=0.062                                           |  P=0.295N                                          |
|FISHER EXACT           |               P=0.619      P=0.382      P=0.131    |               P=0.137      P=0.382      P=0.628N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  5/70 (7%)    9/70 (13%)  11/70 (16%)   9/70 (13%) |
|ADJUSTED (b)           |                                                    |  15.2%        22.8%        23.6%        19.8%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    4/10 (40%)   2/10 (20%) |
|TERMINAL (d)           |                                                    |  4/31 (13%)   4/32 (13%)   5/36 (14%)   5/39 (13%) |
|FIRST INCIDENCE (DAYS) |                                                    |   668          494          463 (I)      463 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.363      P=0.236      P=0.133      P=0.306    |
|INCIDENTAL TUMOR       |                                                    |  P=0.210      P=0.223      P=0.112      P=0.192    |
|LOGISTIC REGRESSION    |                                                    |  P=0.243      P=0.219      P=0.093      P=0.215    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.236                                           |
|FISHER EXACT           |                                                    |               P=0.199      P=0.091      P=0.199    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  19
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/70 (3%)    1/70 (1%)    1/70 (1%)    1/70 (1%)  |
|ADJUSTED (b)           |                                                    |   4.2%         3.1%         2.8%         2.6%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |                                                    |  0/31 (0%)    1/32 (3%)    1/36 (3%)    1/39 (3%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   551          737 (T)      737 (T)      737 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.388N     P=0.499N     P=0.495N     P=0.479N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.373N     P=0.566N     P=0.552N     P=0.472N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.427N     P=0.499N     P=0.500N     P=0.499N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.432N                                          |
|FISHER EXACT           |                                                    |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  7/70 (10%)  10/70 (14%)  11/70 (16%)  10/70 (14%) |
|ADJUSTED (b)           |                                                    |  18.7%        25.5%        23.6%        22.1%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    4/10 (40%)   2/10 (20%) |
|TERMINAL (d)           |                                                    |  4/31 (13%)   5/32 (16%)   5/36 (14%)   6/39 (15%) |
|FIRST INCIDENCE (DAYS) |                                                    |   551          494          463 (I)      463 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.464      P=0.344      P=0.289      P=0.427    |
|INCIDENTAL TUMOR       |                                                    |  P=0.309      P=0.302      P=0.240      P=0.304    |
|LOGISTIC REGRESSION    |                                                    |  P=0.279      P=0.326      P=0.226      P=0.321    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.321                                           |
|FISHER EXACT           |                                                    |               P=0.303      P=0.225      P=0.303    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  20
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   5.9%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/28 (4%)    0/33 (0%)    0/34 (0%)    0/34 (0%)  |  0/31 (0%)    0/32 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   612          ---          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.151N     P=0.222N     P=0.211N     P=0.218N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.214N     P=0.282N     P=0.326N     P=0.326N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.158N     P=0.234N     P=0.227N     P=0.235N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.161N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.248N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 29/70 (41%)  25/70 (36%)  17/70 (24%)  23/70 (33%) | 13/70 (19%)  14/70 (20%)  14/70 (20%)  13/70 (19%) |
|ADJUSTED (b)           |  69.9%        60.6%        41.7%        55.7%      |  30.0%        35.1%        32.3%        29.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           | 16/28 (57%)  17/33 (52%)  11/34 (32%)  16/34 (47%) |  3/31 (10%)   8/32 (25%)   8/36 (22%)   8/39 (21%) |
|FIRST INCIDENCE (DAYS) |   549          533          638          518       |   575          488          425          637       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.060N     P=0.149N     P=0.006N**   P=0.069N   |  P=0.341N     P=0.559      P=0.567N     P=0.437N   |
|INCIDENTAL TUMOR       |  P=0.180N     P=0.357N     P=0.020N*    P=0.310N   |  P=0.310      P=0.469      P=0.334      P=0.138    |
|LOGISTIC REGRESSION    |  P=0.168N     P=0.352N     P=0.016N*    P=0.277N   |  P=0.405      P=0.287      P=0.312      P=0.229    |
|COCHRAN-ARMITAGE       |  P=0.141N                                          |  P=0.508N                                          |
|FISHER EXACT           |               P=0.301N     P=0.024N*    P=0.191N   |               P=0.500      P=0.500      P=0.586N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  21
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma: Benign, Malignant, NOS                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    3/70 (4%)    2/70 (3%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   2.4%         0.0%         8.3%         5.1%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  0/28 (0%)    0/33 (0%)    1/34 (3%)    0/34 (0%)  |  0/31 (0%)    0/32 (0%)    0/36 (0%)    0/39 (0%)  |
|FIRST INCIDENCE (DAYS) |   632          ---          701          653       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.214      P=0.500N     P=0.369      P=0.525    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.121      P=0.617N     P=0.230      P=0.321    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.190      P=0.500N     P=0.332      P=0.502    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.186                                           |    (e)                                             |
|FISHER EXACT           |               P=0.500N     P=0.310      P=0.500    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 56/70 (80%)  57/70 (81%)  55/70 (79%)  57/70 (81%) | 43/70 (61%)  48/70 (69%)  42/70 (60%)  38/70 (54%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  93.3%        93.9%        87.1%        80.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  9/10 (90%)  10/10 (100%)  8/10 (80%)  10/10 (100%)|  3/10 (30%)   4/10 (40%)   5/10 (50%)   3/10 (30%) |
|TERMINAL (d)           | 28/28 (100%) 33/33 (100%) 34/34 (100%) 34/34 (100%)| 28/31 (90%)  29/32 (91%)  30/36 (83%)  30/39 (77%) |
|FIRST INCIDENCE (DAYS) |   459          409          462 (I)      275 (I)   |   450          450          463 (I)      404       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.183N     P=0.257N     P=0.088N     P=0.191N   |  P=0.003N**   P=0.371      P=0.204N     P=0.023N*  |
|INCIDENTAL TUMOR       |  P=0.272      P=0.383      P=0.414N     P=0.228    |  P=0.017N*    P=0.283      P=0.419N     P=0.101N   |
|LOGISTIC REGRESSION    |  P=0.061      P=0.463N     P=0.647      P=0.149    |  P=0.046N*    P=0.312      P=0.506N     P=0.144N   |
|COCHRAN-ARMITAGE       |  P=0.508                                           |  P=0.088N                                          |
|FISHER EXACT           |               P=0.500      P=0.500N     P=0.500    |               P=0.239      P=0.500N     P=0.247N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  22
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        100 PPM      500 PPM      1000 PPM  |   0 PPM        100 PPM      500 PPM      1000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/70 (46%)  28/70 (40%)  27/70 (39%)  30/70 (43%) | 19/70 (27%)  22/70 (31%)  20/70 (29%)  17/70 (24%) |
|ADJUSTED (b)           |  73.7%        64.8%        59.7%        66.5%      |  41.8%        52.4%        44.7%        36.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           | 17/28 (61%)  18/33 (55%)  16/34 (47%)  19/34 (56%) |  6/31 (19%)  13/32 (41%)  12/36 (33%)  10/39 (26%) |
|FIRST INCIDENCE (DAYS) |   549          533          406          439       |   551          488          425          442       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.265N     P=0.153N     P=0.086N     P=0.200N   |  P=0.139N     P=0.437      P=0.520N     P=0.275N   |
|INCIDENTAL TUMOR       |  P=0.397      P=0.432N     P=0.319N     P=0.443    |  P=0.478N     P=0.272      P=0.297      P=0.354    |
|LOGISTIC REGRESSION    |  P=0.424      P=0.422N     P=0.278N     P=0.474    |  P=0.435N     P=0.155      P=0.262      P=0.454    |
|COCHRAN-ARMITAGE       |  P=0.469N                                          |  P=0.277N                                          |
|FISHER EXACT           |               P=0.304N     P=0.247N     P=0.432N   |               P=0.355      P=0.500      P=0.423N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 57/70 (81%)  57/70 (81%)  56/70 (80%)  57/70 (81%) | 50/70 (71%)  51/70 (73%)  50/70 (71%)  46/70 (66%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  96.1%        94.4%        92.5%        88.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/9 (11%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  9/10 (90%)  10/10 (100%)  8/10 (80%)  10/10 (100%)|  3/10 (30%)   4/10 (40%)   5/10 (50%)   3/10 (30%) |
|TERMINAL (d)           | 28/28 (100%) 33/33 (100%) 34/34 (100%) 34/34 (100%)| 29/31 (94%)  29/32 (91%)  32/36 (89%)  33/39 (85%) |
|FIRST INCIDENCE (DAYS) |   459          409          406          275 (I)   |   450          450          425          404       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.163N     P=0.208N     P=0.093N     P=0.151N   |  P=0.020N*    P=0.481N     P=0.262N     P=0.042N*  |
|INCIDENTAL TUMOR       |  P=0.303      P=0.529      P=0.500N     P=0.289    |  P=0.137N     P=0.618      P=0.567      P=0.230N   |
|LOGISTIC REGRESSION    |  P=0.083      P=0.332N     P=0.621      P=0.225    |  P=0.190N     P=0.526N     P=0.569      P=0.173N   |
|COCHRAN-ARMITAGE       |  P=0.523N                                          |  P=0.208N                                          |
|FISHER EXACT           |               P=0.586N     P=0.500N     P=0.586N   |               P=0.500      P=0.574N     P=0.293N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 01                                                 PAGE  23
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- METHLYPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
                                                                           
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   275  462
          Female interim sacrifices(days): 281  463
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.