National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/1648

TDMS Study 05150-02 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                            METHYLPHENIDATE HYDROCHLORIDE                            DATE: 05/20/95       
EXPERIMENT: 05150 TEST: 02                                                                                     TIME: 10:16:51       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65132                              ROUTE: DOSED FEED                                              NTP C#: 56280B       
PATHOLOGIST: A. RUSSFIELD                                                                                      CAS: 298-59-9        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                            METHYLPHENIDATE HYDROCHLORIDE                            DATE: 05/20/95       
EXPERIMENT: 05150 TEST: 02                                                                                     TIME: 10:16:51       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65132                              ROUTE: DOSED FEED                                              NTP C#: 56280B       
PATHOLOGIST: A. RUSSFIELD                                                                                      CAS: 298-59-9        


                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                                    
                                                    ----------------
                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Mason                                            METHYLPHENIDATE HYDROCHLORIDE                            DATE: 05/20/95       
EXPERIMENT: 05150 TEST: 02                                                                                     TIME: 10:16:51       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65132                              ROUTE: DOSED FEED                                              NTP C#: 56280B       
PATHOLOGIST: A. RUSSFIELD                                                                                      CAS: 298-59-9        


                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                 IN THE ANALYSIS OF THE STUDY OF METHYLPHENIDATE HYDROCHLORIDE
              ====================================================================================================
                                                           MALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Harderian Gland               Carcinoma or Adenoma
              Liver                         Hepatoblastoma
                                            Hepatocellular Adenoma
                                            Hepatocellular Carcinoma or Hepatocellular Adenoma
                                            Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
              Lung                          Alveolar/Bronchiolar Adenoma
                                            Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
              All Organs                    Malignant Lymphoma And Histiocytic Sarcoma
                                            Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated
                                             Cell Type
                                            Benign Tumors
              ====================================================================================================
                                                           FEMALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Liver                         Hepatocellular Adenoma
                                            Hepatocellular Carcinoma or Hepatocellular Adenoma
                                            Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
              Lung                          Alveolar/Bronchiolar Adenoma
                                            Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
              Pituitary Gland: Pars Distalis or Unspecified Site
                                            Adenoma
              Thyroid Gland: Follicular Cell
                                            Adenoma
                                            Carcinoma or Adenoma
              All Organs                    Benign Tumors
              ====================================================================================================
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   1
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/69 (3%)    2/69 (3%)    1/70 (1%)    0/70 (0%)  |  0/69 (0%)    0/67 (0%)    0/68 (0%)    1/70 (1%)  |
|ADJUSTED (b)           |   4.4%         4.4%         2.3%         0.0%      |   0.0%         0.0%         0.0%         2.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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%)    0/9 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  2/45 (4%)    2/45 (4%)    1/44 (2%)    0/41 (0%)  |  0/37 (0%)    0/35 (0%)    0/37 (0%)    1/44 (2%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      730 (T)      ---       |   ---          ---          ---          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.127N     P=0.694      P=0.508N     P=0.259N   |  P=0.216        (e)          (e)        P=0.535    |
|INCIDENTAL TUMOR       |  P=0.127N     P=0.695      P=0.508N     P=0.259N   |  P=0.216        (e)          (e)        P=0.535    |
|LOGISTIC REGRESSION    |  P=0.127N     P=0.695      P=0.508N     P=0.259N   |  P=0.216        (e)          (e)        P=0.535    |
|COCHRAN-ARMITAGE       |  P=0.112N                                          |  P=0.191                                           |
|FISHER EXACT           |               P=0.690N     P=0.495N     P=0.245N   |                 (e)          (e)        P=0.504    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    1/70 (1%)    1/70 (1%)    2/69 (3%)  |  0/69 (0%)    0/68 (0%)    1/67 (1%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         2.2%         2.3%         4.9%      |   0.0%         0.0%         2.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (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)           |  0/45 (0%)    1/45 (2%)    1/44 (2%)    2/41 (5%)  |  0/37 (0%)    0/35 (0%)    1/37 (3%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          730 (T)      730 (T)      730 (T)   |   ---          ---          739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.147      P=0.500      P=0.496      P=0.218    |  P=0.673        (e)        P=0.500        (e)      |
|INCIDENTAL TUMOR       |  P=0.147      P=0.500      P=0.496      P=0.218    |  P=0.673        (e)        P=0.500        (e)      |
|LOGISTIC REGRESSION    |  P=0.147      P=0.500      P=0.496      P=0.218    |  P=0.673        (e)        P=0.500        (e)      |
|COCHRAN-ARMITAGE       |  P=0.165                                           |  P=0.650                                           |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.245    |                 (e)        P=0.493        (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   2
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/70 (6%)    1/70 (1%)    0/70 (0%)    1/70 (1%)  |  1/69 (1%)    0/68 (0%)    3/70 (4%)    1/70 (1%)  |
|ADJUSTED (b)           |   8.9%         2.2%         0.0%         2.4%      |   2.7%         0.0%         7.8%         2.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  4/45 (9%)    1/45 (2%)    0/44 (0%)    1/41 (2%)  |  1/37 (3%)    0/35 (0%)    2/37 (5%)    1/44 (2%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      ---          730 (T)   |   739 (T)      ---          708          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.152N     P=0.180N     P=0.066N     P=0.209N   |  P=0.455      P=0.511N     P=0.307      P=0.723N   |
|INCIDENTAL TUMOR       |  P=0.152N     P=0.180N     P=0.066N     P=0.209N   |  P=0.453      P=0.511N     P=0.332      P=0.723N   |
|LOGISTIC REGRESSION    |  P=0.152N     P=0.180N     P=0.066N     P=0.209N   |  P=0.442      P=0.511N     P=0.314      P=0.723N   |
|COCHRAN-ARMITAGE       |  P=0.136N                                          |  P=0.395                                           |
|FISHER EXACT           |               P=0.183N     P=0.060N     P=0.183N   |               P=0.504N     P=0.315      P=0.748N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    0/70 (0%)    1/70 (1%)  |  0/69 (0%)    1/68 (1%)    0/70 (0%)    3/70 (4%)  |
|ADJUSTED (b)           |   2.2%         0.0%         0.0%         2.4%      |   0.0%         2.9%         0.0%         6.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  1/45 (2%)    0/45 (0%)    0/44 (0%)    1/41 (2%)  |  0/37 (0%)    1/35 (3%)    0/37 (0%)    2/44 (5%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      ---          ---          730 (T)   |   ---          739 (T)      ---          677       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.516      P=0.500N     P=0.504N     P=0.741    |  P=0.079      P=0.489        (e)        P=0.152    |
|INCIDENTAL TUMOR       |  P=0.516      P=0.500N     P=0.504N     P=0.741    |  P=0.077      P=0.489        (e)        P=0.144    |
|LOGISTIC REGRESSION    |  P=0.516      P=0.500N     P=0.504N     P=0.741    |  P=0.071      P=0.489        (e)        P=0.138    |
|COCHRAN-ARMITAGE       |  P=0.536                                           |  P=0.057                                           |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.752N   |               P=0.496        (e)        P=0.125    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   3
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/70 (7%)    1/70 (1%)    0/70 (0%)    2/70 (3%)  |  1/69 (1%)    1/68 (1%)    3/70 (4%)    4/70 (6%)  |
|ADJUSTED (b)           |  11.1%         2.2%         0.0%         4.9%      |   2.7%         2.9%         7.8%         8.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  5/45 (11%)   1/45 (2%)    0/44 (0%)    2/41 (5%)  |  1/37 (3%)    1/35 (3%)    2/37 (5%)    3/44 (7%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      ---          730 (T)   |   739 (T)      739 (T)      708          677       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.247N     P=0.104N     P=0.036N*    P=0.256N   |  P=0.107      P=0.749      P=0.307      P=0.233    |
|INCIDENTAL TUMOR       |  P=0.247N     P=0.104N     P=0.036N*    P=0.256N   |  P=0.103      P=0.749      P=0.332      P=0.226    |
|LOGISTIC REGRESSION    |  P=0.247N     P=0.104N     P=0.036N*    P=0.256N   |  P=0.094      P=0.749      P=0.314      P=0.214    |
|COCHRAN-ARMITAGE       |  P=0.219N                                          |  P=0.070                                           |
|FISHER EXACT           |               P=0.104N     P=0.029N*    P=0.221N   |               P=0.748      P=0.315      P=0.187    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/68 (1%)    1/69 (1%)    1/70 (1%)  |  1/68 (1%)    2/67 (3%)    2/69 (3%)    1/70 (1%)  |
|ADJUSTED (b)           |   2.2%         2.2%         2.3%         2.4%      |   2.7%         4.8%         4.7%         2.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  1/45 (2%)    1/45 (2%)    1/44 (2%)    1/41 (2%)  |  1/37 (3%)    0/35 (0%)    0/37 (0%)    1/44 (2%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      730 (T)      730 (T)   |   739 (T)      588          689          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.599      P=0.761      P=0.757      P=0.741    |  P=0.458N     P=0.488      P=0.511      P=0.723N   |
|INCIDENTAL TUMOR       |  P=0.599      P=0.761      P=0.757      P=0.741    |  P=0.597N     P=0.473      P=0.568      P=0.723N   |
|LOGISTIC REGRESSION    |  P=0.599      P=0.761      P=0.757      P=0.741    |  P=0.478N     P=0.485      P=0.506      P=0.723N   |
|COCHRAN-ARMITAGE       |  P=0.622N                                          |  P=0.506N                                          |
|FISHER EXACT           |               P=0.745      P=0.748      P=0.752N   |               P=0.494      P=0.506      P=0.745N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   4
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    2/70 (3%)    1/70 (1%)    0/70 (0%)  |  1/69 (1%)    1/67 (1%)    1/69 (1%)    0/70 (0%)  |
|ADJUSTED (b)           |   6.7%         4.4%         2.3%         0.0%      |   2.4%         2.3%         2.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  3/45 (7%)    2/45 (4%)    1/44 (2%)    0/41 (0%)  |  0/37 (0%)    0/35 (0%)    1/37 (3%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      730 (T)      ---       |   685          603          739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.073N     P=0.500N     P=0.314N     P=0.138N   |  P=0.271N     P=0.750      P=0.753N     P=0.477N   |
|INCIDENTAL TUMOR       |  P=0.073N     P=0.500N     P=0.314N     P=0.138N   |  P=0.430N     P=0.707      P=0.729N     P=0.500N   |
|LOGISTIC REGRESSION    |  P=0.073N     P=0.500N     P=0.314N     P=0.138N   |  P=0.284N     P=0.752      P=0.760N     P=0.487N   |
|COCHRAN-ARMITAGE       |  P=0.064N                                          |  P=0.297N                                          |
|FISHER EXACT           |               P=0.500N     P=0.310N     P=0.122N   |               P=0.744      P=0.752N     P=0.496N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatoblastoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    1/70 (1%)    1/70 (1%)    5/70 (7%)  |  0/69 (0%)    0/67 (0%)    0/69 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         2.2%         2.3%        12.2%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  0/45 (0%)    1/45 (2%)    1/44 (2%)    5/41 (12%) |  0/37 (0%)    0/35 (0%)    0/37 (0%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          730 (T)      730 (T)      730 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.004 **   P=0.500      P=0.496      P=0.026 *  |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.004 **   P=0.500      P=0.496      P=0.026 *  |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.004 **   P=0.500      P=0.496      P=0.026 *  |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.007 **                                        |    (e)                                             |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.029 *  |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   5
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 20/70 (29%)  18/70 (26%)  18/70 (26%)  31/70 (44%) |  7/69 (10%)  11/67 (16%)  11/69 (16%)  29/70 (41%) |
|ADJUSTED (b)           |  41.2%        39.1%        37.5%        65.4%      |  17.7%        28.0%        27.4%        62.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/10 (0%)    1/10 (10%)   2/10 (20%) |  1/10 (10%)   1/10 (10%)   1/10 (10%)   1/10 (10%) |
|TERMINAL (d)           | 17/45 (38%)  17/45 (38%)  15/44 (34%)  25/41 (61%) |  6/37 (16%)   8/35 (23%)   9/37 (24%)  27/44 (61%) |
|FIRST INCIDENCE (DAYS) |   454 (I)      720          274 (I)      454 (I)   |   455 (I)      455 (I)      455 (I)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.003 **   P=0.419N     P=0.453N     P=0.015 *  |  P<0.001 **   P=0.190      P=0.222      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.008 **   P=0.328N     P=0.439N     P=0.031 *  |  P<0.001 **   P=0.177      P=0.230      P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.007 **   P=0.382N     P=0.434N     P=0.026 *  |  P<0.001 **   P=0.178      P=0.224      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.013 *                                         |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.425N     P=0.425N     P=0.039 *  |               P=0.205      P=0.225      P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/70 (14%)   9/70 (13%)  17/70 (24%)  12/70 (17%) |  5/69 (7%)    3/67 (4%)    2/69 (3%)    6/70 (9%)  |
|ADJUSTED (b)           |  20.7%        19.5%        34.7%        24.7%      |  13.5%         8.3%         5.4%        13.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  7/45 (16%)   8/45 (18%)  12/44 (27%)   6/41 (15%) |  5/37 (14%)   2/35 (6%)    2/37 (5%)    5/44 (11%) |
|FIRST INCIDENCE (DAYS) |   537          707          541          454 (I)   |   739 (T)      730          739 (T)      660       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.162      P=0.494N     P=0.095      P=0.357    |  P=0.460      P=0.386N     P=0.215N     P=0.617    |
|INCIDENTAL TUMOR       |  P=0.271      P=0.532N     P=0.086      P=0.452    |  P=0.456      P=0.396N     P=0.215N     P=0.609    |
|LOGISTIC REGRESSION    |  P=0.337      P=0.543N     P=0.088      P=0.514    |  P=0.434      P=0.383N     P=0.215N     P=0.585    |
|COCHRAN-ARMITAGE       |  P=0.216                                           |  P=0.353                                           |
|FISHER EXACT           |               P=0.500N     P=0.099      P=0.408    |               P=0.376N     P=0.220N     P=0.510    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   6
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/70 (14%)  10/70 (14%)  18/70 (26%)  15/70 (21%) |  5/69 (7%)    3/67 (4%)    2/69 (3%)    6/70 (9%)  |
|ADJUSTED (b)           |  20.7%        21.7%        36.7%        31.1%      |  13.5%         8.3%         5.4%        13.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  7/45 (16%)   9/45 (20%)  13/44 (30%)   9/41 (22%) |  5/37 (14%)   2/35 (6%)    2/37 (5%)    5/44 (11%) |
|FIRST INCIDENCE (DAYS) |   537          707          541          454 (I)   |   739 (T)      730          739 (T)      660       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.055      P=0.589N     P=0.067      P=0.155    |  P=0.460      P=0.386N     P=0.215N     P=0.617    |
|INCIDENTAL TUMOR       |  P=0.099      P=0.572      P=0.057      P=0.189    |  P=0.456      P=0.396N     P=0.215N     P=0.609    |
|LOGISTIC REGRESSION    |  P=0.136      P=0.563      P=0.059      P=0.244    |  P=0.434      P=0.383N     P=0.215N     P=0.585    |
|COCHRAN-ARMITAGE       |  P=0.084                                           |  P=0.353                                           |
|FISHER EXACT           |               P=0.595N     P=0.069      P=0.189    |               P=0.376N     P=0.220N     P=0.510    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 26/70 (37%)  23/70 (33%)  28/70 (40%)  37/70 (53%) | 10/69 (14%)  12/67 (18%)  12/69 (17%)  31/70 (44%) |
|ADJUSTED (b)           |  51.6%        48.9%        54.5%        72.2%      |  25.7%        30.0%        30.0%        65.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/10 (0%)    1/10 (10%)   3/10 (30%) |  1/10 (10%)   1/10 (10%)   1/10 (10%)   1/10 (10%) |
|TERMINAL (d)           | 21/45 (47%)  21/45 (47%)  21/44 (48%)  27/41 (66%) |  9/37 (24%)   8/35 (23%)  10/37 (27%)  28/44 (64%) |
|FIRST INCIDENCE (DAYS) |   454 (I)      707          274 (I)      454 (I)   |   455 (I)      455 (I)      455 (I)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.003 **   P=0.351N     P=0.395      P=0.020 *  |  P<0.001 **   P=0.359      P=0.408      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.007 **   P=0.327N     P=0.433      P=0.033 *  |  P<0.001 **   P=0.335      P=0.418      P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.005 **   P=0.310N     P=0.411      P=0.028 *  |  P<0.001 **   P=0.341      P=0.414      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.011 *                                         |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.362N     P=0.431      P=0.044 *  |               P=0.379      P=0.408      P<0.001 ** |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   7
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 26/70 (37%)  23/70 (33%)  28/70 (40%)  37/70 (53%) | 10/69 (14%)  12/67 (18%)  12/69 (17%)  31/70 (44%) |
|ADJUSTED (b)           |  51.6%        48.9%        54.5%        72.2%      |  25.7%        30.0%        30.0%        65.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/10 (0%)    1/10 (10%)   3/10 (30%) |  1/10 (10%)   1/10 (10%)   1/10 (10%)   1/10 (10%) |
|TERMINAL (d)           | 21/45 (47%)  21/45 (47%)  21/44 (48%)  27/41 (66%) |  9/37 (24%)   8/35 (23%)  10/37 (27%)  28/44 (64%) |
|FIRST INCIDENCE (DAYS) |   454 (I)      707          274 (I)      454 (I)   |   455 (I)      455 (I)      455 (I)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.003 **   P=0.351N     P=0.395      P=0.020 *  |  P<0.001 **   P=0.359      P=0.408      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.007 **   P=0.327N     P=0.433      P=0.033 *  |  P<0.001 **   P=0.335      P=0.418      P<0.001 ** |
|LOGISTIC REGRESSION    |  P=0.005 **   P=0.310N     P=0.411      P=0.028 *  |  P<0.001 **   P=0.341      P=0.414      P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.011 *                                         |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.362N     P=0.431      P=0.044 *  |               P=0.379      P=0.408      P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 14/70 (20%)   7/69 (10%)   7/70 (10%)   5/70 (7%)  |  2/68 (3%)    1/68 (1%)    4/69 (6%)    6/70 (9%)  |
|ADJUSTED (b)           |  29.6%        14.8%        15.9%        12.2%      |   4.5%         2.9%        10.8%        13.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/9 (11%)    0/10 (0%)    0/10 (0%)  |  1/10 (10%)   0/10 (0%)    0/9 (0%)     0/10 (0%)  |
|TERMINAL (d)           | 12/45 (27%)   6/45 (13%)   7/44 (16%)   5/41 (12%) |  1/36 (3%)    1/35 (3%)    4/37 (11%)   5/44 (11%) |
|FIRST INCIDENCE (DAYS) |   537          454 (I)      730 (T)      730 (T)   |   455 (I)      739 (T)      739 (T)      690       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.053N     P=0.078N     P=0.082N     P=0.035N*  |  P=0.056      P=0.507N     P=0.340      P=0.198    |
|INCIDENTAL TUMOR       |  P=0.056N     P=0.135N     P=0.076N     P=0.053N   |  P=0.055      P=0.507N     P=0.340      P=0.191    |
|LOGISTIC REGRESSION    |  P=0.041N*    P=0.068N     P=0.076N     P=0.023N*  |  P=0.044 *    P=0.505N     P=0.351      P=0.169    |
|COCHRAN-ARMITAGE       |  P=0.037N*                                         |  P=0.031 *                                         |
|FISHER EXACT           |               P=0.082N     P=0.077N     P=0.023N*  |               P=0.500N     P=0.347      P=0.147    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   8
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/70 (6%)    5/69 (7%)    2/70 (3%)    1/70 (1%)  |  0/68 (0%)    0/68 (0%)    2/69 (3%)    2/70 (3%)  |
|ADJUSTED (b)           |   8.9%        11.1%         4.5%         2.2%      |   0.0%         0.0%         5.3%         4.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  4/45 (9%)    5/45 (11%)   2/44 (5%)    0/41 (0%)  |  0/36 (0%)    0/35 (0%)    1/37 (3%)    2/44 (5%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      730 (T)      684       |   ---          ---          728          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.075N     P=0.500      P=0.347N     P=0.205N   |  P=0.103        (e)        P=0.246      P=0.284    |
|INCIDENTAL TUMOR       |  P=0.059N     P=0.500      P=0.348N     P=0.112N   |  P=0.098        (e)        P=0.274      P=0.284    |
|LOGISTIC REGRESSION    |  P=0.069N     P=0.500      P=0.348N     P=0.187N   |  P=0.096        (e)        P=0.249      P=0.284    |
|COCHRAN-ARMITAGE       |  P=0.061N                                          |  P=0.075                                           |
|FISHER EXACT           |               P=0.491      P=0.340N     P=0.183N   |                 (e)        P=0.252      P=0.255    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/70 (23%)  11/69 (16%)   9/70 (13%)   6/70 (9%)  |  2/68 (3%)    1/68 (1%)    6/69 (9%)    7/70 (10%) |
|ADJUSTED (b)           |  33.9%        23.5%        20.5%        14.1%      |   4.5%         2.9%        15.8%        15.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/9 (11%)    0/10 (0%)    0/10 (0%)  |  1/10 (10%)   0/10 (0%)    0/9 (0%)     0/10 (0%)  |
|TERMINAL (d)           | 14/45 (31%)  10/45 (22%)   9/44 (20%)   5/41 (12%) |  1/36 (3%)    1/35 (3%)    5/37 (14%)   6/44 (14%) |
|FIRST INCIDENCE (DAYS) |   537          454 (I)      730 (T)      684       |   455 (I)      739 (T)      728          690       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.026N*    P=0.193N     P=0.097N     P=0.028N*  |  P=0.029 *    P=0.507N     P=0.141      P=0.133    |
|INCIDENTAL TUMOR       |  P=0.023N*    P=0.290N     P=0.090N     P=0.027N*  |  P=0.028 *    P=0.507N     P=0.152      P=0.127    |
|LOGISTIC REGRESSION    |  P=0.018N*    P=0.173N     P=0.090N     P=0.017N*  |  P=0.022 *    P=0.505N     P=0.146      P=0.109    |
|COCHRAN-ARMITAGE       |  P=0.017N*                                         |  P=0.014 *                                         |
|FISHER EXACT           |               P=0.207N     P=0.092N     P=0.017N*  |               P=0.500N     P=0.142      P=0.090    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE   9
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node                                                                                                                       |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |  0/69 (0%)    0/68 (0%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         4.4%         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%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  0/45 (0%)    2/45 (4%)    0/44 (0%)    0/41 (0%)  |  0/37 (0%)    0/35 (0%)    0/37 (0%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          730 (T)      ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.279N     P=0.239        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.279N     P=0.239        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.279N     P=0.239        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.264N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |  0/69 (0%)    0/68 (0%)    0/70 (0%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         4.4%         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%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  0/45 (0%)    2/45 (4%)    0/44 (0%)    0/41 (0%)  |  0/37 (0%)    0/35 (0%)    0/37 (0%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          730 (T)      ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.279N     P=0.239        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.279N     P=0.239        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.279N     P=0.239        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.264N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  10
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |  0/69 (0%)    0/68 (0%)    2/70 (3%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         4.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  0/45 (0%)    0/45 (0%)    0/44 (0%)    0/41 (0%)  |  0/37 (0%)    0/35 (0%)    1/37 (3%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          469          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.567        (e)        P=0.242        (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.424        (e)        P=0.500        (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.541        (e)        P=0.241        (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.541                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.252        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |  0/69 (0%)    0/68 (0%)    2/70 (3%)    0/70 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         4.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  0/45 (0%)    0/45 (0%)    0/44 (0%)    0/41 (0%)  |  0/37 (0%)    0/35 (0%)    1/37 (3%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          469          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.567        (e)        P=0.242        (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.424        (e)        P=0.500        (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.541        (e)        P=0.241        (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.541                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.252        (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  11
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/65 (3%)    5/67 (7%)    1/69 (1%)    2/67 (3%)  |
|ADJUSTED (b)           |                                                    |   4.6%        11.9%         2.7%         3.8%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/9 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  1/9 (11%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |
|TERMINAL (d)           |                                                    |  1/35 (3%)    2/35 (6%)    1/37 (3%)    0/43 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   455 (I)      391          739 (T)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.219N     P=0.223      P=0.475N     P=0.646N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.340N     P=0.327      P=0.475N     P=0.656N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.252N     P=0.228      P=0.478N     P=0.695    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.259N                                          |
|FISHER EXACT           |                                                    |               P=0.233      P=0.477N     P=0.679N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/68 (0%)    0/68 (0%)    0/64 (0%)    0/64 (0%)  |  7/67 (10%)  10/66 (15%)  15/68 (22%)   9/67 (13%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  18.3%        29.4%        37.9%        19.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/9 (0%)     0/9 (0%)     0/10 (0%)    1/10 (10%) |
|TERMINAL (d)           |  0/44 (0%)    0/44 (0%)    0/38 (0%)    0/37 (0%)  |  6/37 (16%)  10/34 (29%)  12/36 (33%)   7/42 (17%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   708          739 (T)      686          455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.531      P=0.229      P=0.045 *    P=0.499    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.522      P=0.234      P=0.060      P=0.487    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.468      P=0.234      P=0.047 *    P=0.443    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.367                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.291      P=0.055      P=0.395    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  12
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Seminal Vesicle                                                                                                                  |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/70 (0%)  |                                                    |
|ADJUSTED (b)           |   0.0%         4.4%         0.0%         0.0%      |                                                    |
|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)           |  0/45 (0%)    2/45 (4%)    0/44 (0%)    0/41 (0%)  |                                                    |
|FIRST INCIDENCE (DAYS) |   ---          730 (T)      ---          ---       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.279N     P=0.239        (e)          (e)      |                                                    |
|INCIDENTAL TUMOR       |  P=0.279N     P=0.239        (e)          (e)      |                                                    |
|LOGISTIC REGRESSION    |  P=0.279N     P=0.239        (e)          (e)      |                                                    |
|COCHRAN-ARMITAGE       |  P=0.264N                                          |                                                    |
|FISHER EXACT           |               P=0.248        (e)          (e)      |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/70 (0%)    0/70 (0%)    1/70 (1%)  |  0/69 (0%)    1/68 (1%)    1/70 (1%)    1/70 (1%)  |
|ADJUSTED (b)           |   4.3%         0.0%         0.0%         2.4%      |   0.0%         2.9%         2.7%         2.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  1/45 (2%)    0/45 (0%)    0/44 (0%)    1/41 (2%)  |  0/37 (0%)    1/35 (3%)    1/37 (3%)    1/44 (2%)  |
|FIRST INCIDENCE (DAYS) |   640          ---          ---          730 (T)   |   ---          739 (T)      739 (T)      739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.549N     P=0.235N     P=0.247N     P=0.522N   |  P=0.468      P=0.489      P=0.500      P=0.535    |
|INCIDENTAL TUMOR       |  P=0.509N     P=0.353N     P=0.211N     P=0.522N   |  P=0.468      P=0.489      P=0.500      P=0.535    |
|LOGISTIC REGRESSION    |  P=0.536N     P=0.235N     P=0.240N     P=0.505N   |  P=0.468      P=0.489      P=0.500      P=0.535    |
|COCHRAN-ARMITAGE       |  P=0.529N                                          |  P=0.419                                           |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.500N   |               P=0.496      P=0.504      P=0.504    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  13
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    0/70 (0%)    0/70 (0%)    0/70 (0%)  |  0/69 (0%)    1/68 (1%)    1/70 (1%)    1/70 (1%)  |
|ADJUSTED (b)           |   4.3%         0.0%         0.0%         0.0%      |   0.0%         2.9%         2.7%         2.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  1/45 (2%)    0/45 (0%)    0/44 (0%)    0/41 (0%)  |  0/37 (0%)    1/35 (3%)    1/37 (3%)    1/44 (2%)  |
|FIRST INCIDENCE (DAYS) |   640          ---          ---          ---       |   ---          739 (T)      739 (T)      739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.169N     P=0.235N     P=0.247N     P=0.250N   |  P=0.468      P=0.489      P=0.500      P=0.535    |
|INCIDENTAL TUMOR       |  P=0.137N     P=0.353N     P=0.211N     P=0.250N   |  P=0.468      P=0.489      P=0.500      P=0.535    |
|LOGISTIC REGRESSION    |  P=0.163N     P=0.235N     P=0.240N     P=0.240N   |  P=0.468      P=0.489      P=0.500      P=0.535    |
|COCHRAN-ARMITAGE       |  P=0.161N                                          |  P=0.419                                           |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.248N   |               P=0.496      P=0.504      P=0.504    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/69 (1%)    0/69 (0%)    1/69 (1%)    3/70 (4%)  |  2/68 (3%)    0/67 (0%)    1/68 (1%)    0/70 (0%)  |
|ADJUSTED (b)           |   2.2%         0.0%         2.3%         7.0%      |   5.4%         0.0%         2.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/9 (0%)     0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |
|TERMINAL (d)           |  1/45 (2%)    0/45 (0%)    1/43 (2%)    2/41 (5%)  |  2/37 (5%)    0/35 (0%)    1/37 (3%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      ---          730 (T)      684       |   739 (T)      ---          739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.065      P=0.500N     P=0.751      P=0.283    |  P=0.218N     P=0.251N     P=0.500N     P=0.201N   |
|INCIDENTAL TUMOR       |  P=0.101      P=0.500N     P=0.751      P=0.409    |  P=0.218N     P=0.251N     P=0.500N     P=0.201N   |
|LOGISTIC REGRESSION    |  P=0.070      P=0.500N     P=0.751      P=0.297    |  P=0.218N     P=0.251N     P=0.500N     P=0.201N   |
|COCHRAN-ARMITAGE       |  P=0.078                                           |  P=0.247N                                          |
|FISHER EXACT           |               P=0.500N     P=0.752N     P=0.315    |               P=0.252N     P=0.500N     P=0.241N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  14
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    2/70 (3%)    0/70 (0%)  |                                                    |
|ADJUSTED (b)           |   0.0%         0.0%         4.5%         0.0%      |                                                    |
|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)           |  0/45 (0%)    0/45 (0%)    2/44 (5%)    0/41 (0%)  |                                                    |
|FIRST INCIDENCE (DAYS) |   ---          ---          730 (T)      ---       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.516        (e)        P=0.234        (e)      |                                                    |
|INCIDENTAL TUMOR       |  P=0.516        (e)        P=0.234        (e)      |                                                    |
|LOGISTIC REGRESSION    |  P=0.516        (e)        P=0.234        (e)      |                                                    |
|COCHRAN-ARMITAGE       |  P=0.536                                           |                                                    |
|FISHER EXACT           |                 (e)        P=0.248        (e)      |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/69 (1%)    0/69 (0%)    0/70 (0%)  |  0/69 (0%)    6/66 (9%)    0/68 (0%)    4/69 (6%)  |
|ADJUSTED (b)           |   2.2%         2.2%         0.0%         0.0%      |   0.0%        17.1%         0.0%         9.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/45 (2%)    1/45 (2%)    0/44 (0%)    0/41 (0%)  |  0/37 (0%)    6/35 (17%)   0/37 (0%)    3/43 (7%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      ---          ---       |   ---          739 (T)      ---          677       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.221N     P=0.761      P=0.504N     P=0.519N   |  P=0.475      P=0.014 *      (e)        P=0.084    |
|INCIDENTAL TUMOR       |  P=0.221N     P=0.761      P=0.504N     P=0.519N   |  P=0.474      P=0.014 *      (e)        P=0.080    |
|LOGISTIC REGRESSION    |  P=0.221N     P=0.761      P=0.504N     P=0.519N   |  P=0.454      P=0.014 *      (e)        P=0.074    |
|COCHRAN-ARMITAGE       |  P=0.208N                                          |  P=0.397                                           |
|FISHER EXACT           |               P=0.748      P=0.504N     P=0.500N   |               P=0.012 *      (e)        P=0.060    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  15
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/69 (1%)    0/69 (0%)    0/70 (0%)  |  0/69 (0%)    6/66 (9%)    1/68 (1%)    4/69 (6%)  |
|ADJUSTED (b)           |   2.2%         2.2%         0.0%         0.0%      |   0.0%        17.1%         2.7%         9.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/10 (0%)  |
|TERMINAL (d)           |  1/45 (2%)    1/45 (2%)    0/44 (0%)    0/41 (0%)  |  0/37 (0%)    6/35 (17%)   1/37 (3%)    3/43 (7%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      ---          ---       |   ---          739 (T)      739 (T)      677       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.221N     P=0.761      P=0.504N     P=0.519N   |  P=0.454      P=0.014 *    P=0.500      P=0.084    |
|INCIDENTAL TUMOR       |  P=0.221N     P=0.761      P=0.504N     P=0.519N   |  P=0.453      P=0.014 *    P=0.500      P=0.080    |
|LOGISTIC REGRESSION    |  P=0.221N     P=0.761      P=0.504N     P=0.519N   |  P=0.433      P=0.014 *    P=0.500      P=0.074    |
|COCHRAN-ARMITAGE       |  P=0.208N                                          |  P=0.373                                           |
|FISHER EXACT           |               P=0.748      P=0.504N     P=0.500N   |               P=0.012 *    P=0.496      P=0.060    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/69 (3%)    0/68 (0%)    6/70 (9%)    1/70 (1%)  |
|ADJUSTED (b)           |                                                    |   5.1%         0.0%        15.6%         2.3%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/9 (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)           |                                                    |  1/37 (3%)    0/35 (0%)    5/37 (14%)   1/44 (2%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   708          ---          705          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.538      P=0.258N     P=0.139      P=0.449N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.537      P=0.266N     P=0.159      P=0.460N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.522      P=0.250N     P=0.142      P=0.460N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.460                                           |
|FISHER EXACT           |                                                    |               P=0.252N     P=0.142      P=0.495N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  16
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    1/70 (1%)    0/70 (0%)  |  2/69 (3%)    0/68 (0%)    3/70 (4%)    1/70 (1%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.3%         0.0%      |   5.4%         0.0%         7.5%         2.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  0/45 (0%)    0/45 (0%)    1/44 (2%)    0/41 (0%)  |  2/37 (5%)    0/35 (0%)    2/37 (5%)    1/44 (2%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          730 (T)      ---       |   739 (T)      ---          656          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.637        (e)        P=0.496        (e)      |  P=0.567N     P=0.251N     P=0.504      P=0.440N   |
|INCIDENTAL TUMOR       |  P=0.637        (e)        P=0.496        (e)      |  P=0.571N     P=0.251N     P=0.526      P=0.440N   |
|LOGISTIC REGRESSION    |  P=0.637        (e)        P=0.496        (e)      |  P=0.590N     P=0.251N     P=0.510      P=0.440N   |
|COCHRAN-ARMITAGE       |  P=0.649                                           |  P=0.571                                           |
|FISHER EXACT           |                 (e)        P=0.500        (e)      |               P=0.252N     P=0.507      P=0.495N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/70 (6%)    3/70 (4%)    1/70 (1%)    3/70 (4%)  |  3/69 (4%)    1/68 (1%)    2/70 (3%)    0/70 (0%)  |
|ADJUSTED (b)           |   8.9%         6.7%         2.3%         7.0%      |   7.7%         2.3%         5.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  4/45 (9%)    3/45 (7%)    1/44 (2%)    2/41 (5%)  |  2/37 (5%)    0/35 (0%)    2/37 (5%)    0/44 (0%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      730 (T)      684       |   685          603          739 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.436N     P=0.500N     P=0.187N     P=0.543N   |  P=0.107N     P=0.326N     P=0.494N     P=0.097N   |
|INCIDENTAL TUMOR       |  P=0.382N     P=0.500N     P=0.187N     P=0.430N   |  P=0.151N     P=0.334N     P=0.474N     P=0.103N   |
|LOGISTIC REGRESSION    |  P=0.419N     P=0.500N     P=0.187N     P=0.517N   |  P=0.115N     P=0.322N     P=0.489N     P=0.103N   |
|COCHRAN-ARMITAGE       |  P=0.392N                                          |  P=0.131N                                          |
|FISHER EXACT           |               P=0.500N     P=0.183N     P=0.500N   |               P=0.315N     P=0.493N     P=0.120N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  17
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/70 (6%)    3/70 (4%)    2/70 (3%)    3/70 (4%)  |  4/69 (6%)    1/68 (1%)    5/70 (7%)    1/70 (1%)  |
|ADJUSTED (b)           |   8.9%         6.7%         4.5%         7.0%      |  10.3%         2.3%        12.8%         2.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  4/45 (9%)    3/45 (7%)    2/44 (5%)    2/41 (5%)  |  3/37 (8%)    0/35 (0%)    4/37 (11%)   1/44 (2%)  |
|FIRST INCIDENCE (DAYS) |   730 (T)      730 (T)      730 (T)      684       |   685          603          656          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.473N     P=0.500N     P=0.347N     P=0.543N   |  P=0.254N     P=0.200N     P=0.508      P=0.137N   |
|INCIDENTAL TUMOR       |  P=0.420N     P=0.500N     P=0.348N     P=0.430N   |  P=0.321N     P=0.205N     P=0.540      P=0.143N   |
|LOGISTIC REGRESSION    |  P=0.456N     P=0.500N     P=0.348N     P=0.517N   |  P=0.278N     P=0.195N     P=0.515      P=0.147N   |
|COCHRAN-ARMITAGE       |  P=0.426N                                          |  P=0.323N                                          |
|FISHER EXACT           |               P=0.500N     P=0.340N     P=0.500N   |               P=0.187N     P=0.509      P=0.178N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    1/70 (1%)    0/70 (0%)    1/70 (1%)  |  2/69 (3%)    1/68 (1%)    2/70 (3%)    2/70 (3%)  |
|ADJUSTED (b)           |   0.0%         2.0%         0.0%         2.4%      |   5.4%         2.9%         4.3%         4.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  0/45 (0%)    0/45 (0%)    0/44 (0%)    0/41 (0%)  |  2/37 (5%)    1/35 (3%)    0/37 (0%)    2/44 (5%)  |
|FIRST INCIDENCE (DAYS) |   ---          674          ---          707       |   739 (T)      739 (T)      578          739 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.447      P=0.513        (e)        P=0.486    |  P=0.556      P=0.519N     P=0.686N     P=0.631N   |
|INCIDENTAL TUMOR       |  P=0.632N     P=0.773        (e)        P=0.846    |  P=0.446      P=0.519N     P=0.660      P=0.631N   |
|LOGISTIC REGRESSION    |  P=0.460      P=0.502        (e)        P=0.497    |  P=0.527      P=0.519N     P=0.689N     P=0.631N   |
|COCHRAN-ARMITAGE       |  P=0.464                                           |  P=0.490                                           |
|FISHER EXACT           |               P=0.500        (e)        P=0.500    |               P=0.506N     P=0.685N     P=0.685N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  18
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    6/70 (9%)    3/70 (4%)   10/70 (14%) | 14/69 (20%)  14/68 (21%)  10/70 (14%)  18/70 (26%) |
|ADJUSTED (b)           |   6.4%        12.6%         6.6%        22.6%      |  33.8%        36.4%        23.0%        40.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  2/45 (4%)    4/45 (9%)    2/44 (5%)    7/41 (17%) | 10/37 (27%)  11/35 (31%)   6/37 (16%)  17/44 (39%) |
|FIRST INCIDENCE (DAYS) |   617          674          626          654       |   621          625          183          690       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.031 *    P=0.255      P=0.645      P=0.032 *  |  P=0.484      P=0.515      P=0.248N     P=0.466    |
|INCIDENTAL TUMOR       |  P=0.095      P=0.316      P=0.627N     P=0.089    |  P=0.313      P=0.497      P=0.239N     P=0.358    |
|LOGISTIC REGRESSION    |  P=0.076      P=0.255      P=0.658      P=0.035 *  |  P=0.394      P=0.519      P=0.230N     P=0.400    |
|COCHRAN-ARMITAGE       |  P=0.043 *                                         |  P=0.278                                           |
|FISHER EXACT           |               P=0.247      P=0.660N     P=0.039 *  |               P=0.567      P=0.238N     P=0.289    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated                                               |
|     Cell Type                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/70 (4%)    5/70 (7%)    3/70 (4%)    9/70 (13%) | 12/69 (17%)  13/68 (19%)   8/70 (11%)  17/70 (24%) |
|ADJUSTED (b)           |   6.4%        10.8%         6.6%        20.7%      |  28.9%        33.8%        19.5%        37.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           |  2/45 (4%)    4/45 (9%)    2/44 (5%)    7/41 (17%) |  8/37 (22%)  10/35 (29%)   6/37 (16%)  16/44 (36%) |
|FIRST INCIDENCE (DAYS) |   617          708          626          654       |   621          625          183          690       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.038 *    P=0.363      P=0.645      P=0.052    |  P=0.410      P=0.436      P=0.232N     P=0.361    |
|INCIDENTAL TUMOR       |  P=0.085      P=0.367      P=0.627N     P=0.103    |  P=0.281      P=0.412      P=0.212N     P=0.256    |
|LOGISTIC REGRESSION    |  P=0.044 *    P=0.371      P=0.658      P=0.059    |  P=0.330      P=0.435      P=0.216N     P=0.299    |
|COCHRAN-ARMITAGE       |  P=0.053                                           |  P=0.229                                           |
|FISHER EXACT           |               P=0.359      P=0.660N     P=0.064    |               P=0.484      P=0.224N     P=0.215    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  19
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 33/70 (47%)  24/70 (34%)  25/70 (36%)  35/70 (50%) | 22/69 (32%)  26/68 (38%)  31/70 (44%)  38/70 (54%) |
|ADJUSTED (b)           |  65.7%        50.8%        52.6%        74.0%      |  51.4%        62.6%        71.7%        75.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   1/10 (10%)   1/10 (10%)   2/10 (20%) |  3/10 (30%)   1/10 (10%)   1/10 (10%)   3/10 (30%) |
|TERMINAL (d)           | 28/45 (62%)  22/45 (49%)  22/44 (50%)  29/41 (71%) | 17/37 (46%)  20/35 (57%)  25/37 (68%)  32/44 (73%) |
|FIRST INCIDENCE (DAYS) |   454 (I)      454 (I)      274 (I)      454 (I)   |   455 (I)      391          455 (I)      455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.072      P=0.068N     P=0.122N     P=0.252    |  P=0.030 *    P=0.214      P=0.071      P=0.025 *  |
|INCIDENTAL TUMOR       |  P=0.116      P=0.069N     P=0.108N     P=0.310    |  P=0.011 *    P=0.253      P=0.083      P=0.019 *  |
|LOGISTIC REGRESSION    |  P=0.135      P=0.050N*    P=0.102N     P=0.402    |  P=0.007 **   P=0.205      P=0.069      P=0.008 ** |
|COCHRAN-ARMITAGE       |  P=0.190                                           |  P=0.004 **                                        |
|FISHER EXACT           |               P=0.084N     P=0.115N     P=0.433    |               P=0.274      P=0.092      P=0.006 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 19/70 (27%)  24/70 (34%)  22/70 (31%)  25/70 (36%) | 22/69 (32%)  21/68 (31%)  16/70 (23%)  26/70 (37%) |
|ADJUSTED (b)           |  38.0%        48.9%        44.0%        50.6%      |  52.2%        50.8%        36.1%        54.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (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)           | 14/45 (31%)  20/45 (44%)  16/44 (36%)  17/41 (41%) | 17/37 (46%)  15/35 (43%)  10/37 (27%)  22/44 (50%) |
|FIRST INCIDENCE (DAYS) |   537          628          541          454 (I)   |   621          462          183          648       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.151      P=0.244      P=0.329      P=0.129    |  P=0.484N     P=0.558      P=0.167N     P=0.565    |
|INCIDENTAL TUMOR       |  P=0.333      P=0.164      P=0.383      P=0.204    |  P=0.335      P=0.544N     P=0.096N     P=0.448    |
|LOGISTIC REGRESSION    |  P=0.387      P=0.246      P=0.333      P=0.242    |  P=0.456      P=0.566      P=0.141N     P=0.465    |
|COCHRAN-ARMITAGE       |  P=0.242                                           |  P=0.305                                           |
|FISHER EXACT           |               P=0.232      P=0.355      P=0.181    |               P=0.523N     P=0.158N     P=0.318    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05150 TEST: 02                                                 PAGE  20
                        STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- METHYLPHENIDATE HYDROCHLORIDE
                                                 MALE TERMINAL SACRIFICE AT 105 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 106 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        50 PPM       250 PPM      500 PPM   |   0 PPM        50 PPM       250 PPM      500 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 43/70 (61%)  36/70 (51%)  35/70 (50%)  46/70 (66%) | 37/69 (54%)  37/68 (54%)  41/70 (59%)  44/70 (63%) |
|ADJUSTED (b)           |  82.6%        70.5%        67.0%        88.3%      |  78.4%        76.8%        85.2%        86.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   1/10 (10%)   1/10 (10%)   3/10 (30%) |  3/10 (30%)   1/10 (10%)   1/10 (10%)   3/10 (30%) |
|TERMINAL (d)           | 36/45 (80%)  30/45 (67%)  27/44 (61%)  35/41 (85%) | 27/37 (73%)  24/35 (69%)  30/37 (81%)  37/44 (84%) |
|FIRST INCIDENCE (DAYS) |   454 (I)      454 (I)      274 (I)      454 (I)   |   455 (I)      103          183          455 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.063      P=0.132N     P=0.143N     P=0.163    |  P=0.507      P=0.440      P=0.317      P=0.509    |
|INCIDENTAL TUMOR       |  P=0.178      P=0.092N     P=0.061N     P=0.312    |  P=0.115      P=0.574      P=0.390      P=0.292    |
|LOGISTIC REGRESSION    |  P=0.114      P=0.073N     P=0.089N     P=0.305    |  P=0.230      P=0.439      P=0.302      P=0.267    |
|COCHRAN-ARMITAGE       |  P=0.191                                           |  P=0.122                                           |
|FISHER EXACT           |               P=0.153N     P=0.117N     P=0.363    |               P=0.531      P=0.338      P=0.176    |
|=================================================================================================================================|
 (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):   274  454
          Female interim sacrifices(days): 280  455
 (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.