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TDMS Study 05068-09 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Microbiological Assoc.                                     CODEINE                                        DATE: 04/02/96       
EXPERIMENT: 05068 TEST: 09                                                                                     TIME: 17:43:44       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-75178                              ROUTE: DOSED FEED                                              NTP C#: 61541B       
PATHOLOGIST: L. BRENNECKE                                                                                      CAS: 76-57-3         
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Microbiological Assoc.                                     CODEINE                                        DATE: 04/02/96       
EXPERIMENT: 05068 TEST: 09                                                                                     TIME: 17:43:44       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-75178                              ROUTE: DOSED FEED                                              NTP C#: 61541B       
PATHOLOGIST: L. BRENNECKE                                                                                      CAS: 76-57-3         




                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                                    

                                                    ----------------

                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Clitoral/Preputial Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Microbiological Assoc.                                     CODEINE                                        DATE: 04/02/96       
EXPERIMENT: 05068 TEST: 09                                                                                     TIME: 17:43:44       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-75178                              ROUTE: DOSED FEED                                              NTP C#: 61541B       
PATHOLOGIST: L. BRENNECKE                                                                                      CAS: 76-57-3         




                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                            IN THE ANALYSIS OF THE STUDY OF CODEINE

              ====================================================================================================

                                                           MALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------

              Adrenal Medulla               Pheochromocytoma Benign
                                            Pheochromocytoma: Benign, Complex, Malignant, NOS
              Clitoral/Preputial Gland      Carcinoma or Adenoma
              Testes                        Adenoma
              All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated

              ====================================================================================================

                                                           FEMALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------

              Clitoral/Preputial Gland      Adenoma
                                            Carcinoma or Adenoma
              Mammary Gland                 Fibroadenoma
                                            Fibroma, Fibroadenoma, Carcinoma, or Adenoma
              Pituitary Gland: Pars Distalis or Unspecified Site
                                            Adenoma
                                            Carcinoma or Adenoma
              Uterus                        Polyp Stromal
                                            Sarcoma Stromal or Polyp Stromal
              All Organs                    Benign Tumors
                                            Malignant Tumors
                                            Malignant and Benign Tumors

              ====================================================================================================
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   1
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/59 (27%)   7/60 (12%)   6/59 (10%)   3/60 (5%)  |  2/60 (3%)    5/60 (8%)    1/59 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |  49.1%        26.2%        21.7%        13.6%      |   6.6%        12.2%         2.7%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 12/28 (43%)   3/20 (15%)   3/21 (14%)   2/20 (10%) |  1/28 (4%)    3/38 (8%)    0/28 (0%)    1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   599          455 (I)      608          708       |   677          689          686          733 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.005N**   P=0.114N     P=0.051N     P=0.007N** |  P=0.171N     P=0.362      P=0.457N     P=0.438N   |
|INCIDENTAL TUMOR       |  P=0.001N**   P=0.025N*    P=0.012N*    P=0.002N** |  P=0.104N     P=0.320      P=0.310N     P=0.391N   |
|LOGISTIC REGRESSION    |  P<0.001N**   P=0.025N*    P=0.011N*    P=0.001N** |  P=0.155N     P=0.314      P=0.464N     P=0.432N   |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.196N                                          |
|FISHER EXACT           |               P=0.028N*    P=0.016N*    P<0.001N** |               P=0.219      P=0.506N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/59 (27%)   7/60 (12%)   7/59 (12%)   3/60 (5%)  |  3/60 (5%)    5/60 (8%)    1/59 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |  49.1%        26.2%        24.5%        13.6%      |  10.0%        12.2%         2.7%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   0/9 (0%)     0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 12/28 (43%)   3/20 (15%)   3/21 (14%)   2/20 (10%) |  2/28 (7%)    3/38 (8%)    0/28 (0%)    1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   599          455 (I)      608          708       |   677          689          686          733 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.006N**   P=0.114N     P=0.089N     P=0.007N** |  P=0.099N     P=0.535      P=0.275N     P=0.249N   |
|INCIDENTAL TUMOR       |  P=0.001N**   P=0.025N*    P=0.020N*    P=0.002N** |  P=0.056N     P=0.498      P=0.170N     P=0.215N   |
|LOGISTIC REGRESSION    |  P=0.001N**   P=0.025N*    P=0.022N*    P=0.001N** |  P=0.085N     P=0.490      P=0.264N     P=0.233N   |
|COCHRAN-ARMITAGE       |  P=0.001N**                                        |  P=0.116N                                          |
|FISHER EXACT           |               P=0.028N*    P=0.031N*    P<0.001N** |               P=0.359      P=0.316N     P=0.309N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   2
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/59 (5%)    6/60 (10%)   7/58 (12%)   2/59 (3%)  |  5/57 (9%)    6/57 (11%)  12/59 (20%)   1/60 (2%)  |
|ADJUSTED (b)           |   9.1%        20.6%        26.8%         7.4%      |  16.7%        15.7%        37.8%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/9 (0%)     0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/29 (7%)    2/20 (10%)   3/20 (15%)   1/20 (5%)  |  3/27 (11%)   5/36 (14%)  10/29 (34%)   1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   567          586          655          582       |   663          546          662          733 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.463N     P=0.171      P=0.090      P=0.604N   |  P=0.115N     P=0.566N     P=0.081      P=0.071N   |
|INCIDENTAL TUMOR       |  P=0.331N     P=0.325      P=0.193      P=0.549N   |  P=0.084N     P=0.611N     P=0.154      P=0.036N*  |
|LOGISTIC REGRESSION    |  P=0.363N     P=0.246      P=0.136      P=0.507N   |  P=0.077N     P=0.627      P=0.113      P=0.053N   |
|COCHRAN-ARMITAGE       |  P=0.344N                                          |  P=0.130N                                          |
|FISHER EXACT           |               P=0.254      P=0.154      P=0.500N   |               P=0.500      P=0.066      P=0.092N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/59 (5%)    6/60 (10%)   8/58 (14%)   2/59 (3%)  |  6/57 (11%)   6/57 (11%)  12/59 (20%)   1/60 (2%)  |
|ADJUSTED (b)           |   9.1%        20.6%        31.1%         7.4%      |  19.0%        15.7%        37.8%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/9 (0%)     0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/29 (7%)    2/20 (10%)   4/20 (20%)   1/20 (5%)  |  3/27 (11%)   5/36 (14%)  10/29 (34%)   1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   567          586          655          582       |   587          546          662          733 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.491N     P=0.171      P=0.049 *    P=0.604N   |  P=0.075N     P=0.430N     P=0.145      P=0.037N*  |
|INCIDENTAL TUMOR       |  P=0.361N     P=0.325      P=0.111      P=0.549N   |  P=0.060N     P=0.581N     P=0.219      P=0.026N*  |
|LOGISTIC REGRESSION    |  P=0.385N     P=0.246      P=0.081      P=0.507N   |  P=0.049N*    P=0.514N     P=0.190      P=0.031N*  |
|COCHRAN-ARMITAGE       |  P=0.363N                                          |  P=0.087N                                          |
|FISHER EXACT           |               P=0.254      P=0.097      P=0.500N   |               P=0.619N     P=0.114      P=0.049N*  |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   3
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Ear                                                                                                                              |
|     Schwannoma Malignant                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    1/60 (2%)    1/60 (2%)    2/60 (3%)  |  0/60 (0%)    0/60 (0%)    2/60 (3%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         3.7%         3.8%         8.4%      |   0.0%         0.0%         6.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    0/20 (0%)    0/21 (0%)    1/20 (5%)  |  0/28 (0%)    0/38 (0%)    2/29 (7%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          695          720          701       |   ---          ---          733 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.133      P=0.472      P=0.471      P=0.192    |  P=0.601        (e)        P=0.246        (e)      |
|INCIDENTAL TUMOR       |  P=0.179      P=0.650      P=0.625      P=0.260    |  P=0.601        (e)        P=0.246        (e)      |
|LOGISTIC REGRESSION    |  P=0.139      P=0.496      P=0.490      P=0.216    |  P=0.601        (e)        P=0.246        (e)      |
|COCHRAN-ARMITAGE       |  P=0.153                                           |  P=0.595                                           |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.248    |                 (e)        P=0.248        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    3/60 (5%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    1/60 (2%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        11.3%         0.0%         0.0%      |   0.0%         2.0%         3.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    1/20 (5%)    0/21 (0%)    0/20 (0%)  |  0/28 (0%)    0/38 (0%)    1/29 (3%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          658          ---          ---       |   ---          479          733 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.339N     P=0.094        (e)          (e)      |  P=0.590N     P=0.513      P=0.507        (e)      |
|INCIDENTAL TUMOR       |  P=0.276N     P=0.184        (e)          (e)      |  P=0.673N     P=0.419      P=0.507        (e)      |
|LOGISTIC REGRESSION    |  P=0.320N     P=0.116        (e)          (e)      |  P=0.614N     P=0.422      P=0.507        (e)      |
|COCHRAN-ARMITAGE       |  P=0.312N                                          |  P=0.595N                                          |
|FISHER EXACT           |               P=0.122        (e)          (e)      |               P=0.500      P=0.500        (e)      |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   4
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    3/60 (5%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    1/60 (2%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%        11.3%         0.0%         0.0%      |   3.6%         2.0%         3.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    1/20 (5%)    0/21 (0%)    0/20 (0%)  |  1/28 (4%)    0/38 (0%)    1/29 (3%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          658          ---          ---       |   733 (T)      479          733 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.339N     P=0.094        (e)          (e)      |  P=0.305N     P=0.719N     P=0.754N     P=0.473N   |
|INCIDENTAL TUMOR       |  P=0.276N     P=0.184        (e)          (e)      |  P=0.376N     P=0.753      P=0.754N     P=0.473N   |
|LOGISTIC REGRESSION    |  P=0.320N     P=0.116        (e)          (e)      |  P=0.314N     P=0.742      P=0.754N     P=0.473N   |
|COCHRAN-ARMITAGE       |  P=0.312N                                          |  P=0.312N                                          |
|FISHER EXACT           |               P=0.122        (e)          (e)      |               P=0.752N     P=0.752N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/60 (0%)    0/60 (0%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   6.9%         0.0%         0.0%         5.0%      |   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%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/29 (7%)    0/20 (0%)    0/21 (0%)    1/20 (5%)  |  0/28 (0%)    0/38 (0%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          ---          732 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.542N     P=0.323N     P=0.311N     P=0.630N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.542N     P=0.323N     P=0.311N     P=0.630N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.542N     P=0.323N     P=0.311N     P=0.630N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.461N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248N     P=0.248N     P=0.500N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   5
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    0/60 (0%)    0/60 (0%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |  10.3%         0.0%         0.0%         5.0%      |   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%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/29 (10%)   0/20 (0%)    0/21 (0%)    1/20 (5%)  |  0/28 (0%)    0/38 (0%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          ---          732 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.327N     P=0.192N     P=0.182N     P=0.445N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.327N     P=0.192N     P=0.182N     P=0.445N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.327N     P=0.192N     P=0.182N     P=0.445N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.248N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.122N     P=0.122N     P=0.309N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    0/60 (0%)    0/60 (0%)    1/60 (2%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |  10.3%         0.0%         0.0%         5.0%      |   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%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/29 (10%)   0/20 (0%)    0/21 (0%)    1/20 (5%)  |  0/28 (0%)    0/38 (0%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          ---          732 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.327N     P=0.192N     P=0.182N     P=0.445N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.327N     P=0.192N     P=0.182N     P=0.445N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.327N     P=0.192N     P=0.182N     P=0.445N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.248N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.122N     P=0.122N     P=0.309N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   6
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    0/59 (0%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   3.5%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%         2.9%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    0/20 (0%)    0/21 (0%)    0/20 (0%)  |  0/28 (0%)    0/38 (0%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   446          ---          ---          ---       |   ---          ---          ---          719       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.115N     P=0.253N     P=0.236N     P=0.240N   |  P=0.207        (e)          (e)        P=0.538    |
|INCIDENTAL TUMOR       |  P=0.110N     P=0.350N     P=0.295N     P=0.220N   |  P=0.269        (e)          (e)        P=0.638    |
|LOGISTIC REGRESSION    |  P=0.157N     P=0.308N     P=0.354N     P=0.289N   |  P=0.210        (e)          (e)        P=0.542    |
|COCHRAN-ARMITAGE       |  P=0.115N                                          |  P=0.199                                           |
|FISHER EXACT           |               P=0.252N     P=0.248N     P=0.248N   |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/59 (3%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    0/60 (0%)    0/60 (0%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         6.6%         0.0%         0.0%      |   3.6%         0.0%         0.0%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    1/20 (5%)    0/21 (0%)    0/20 (0%)  |  1/28 (4%)    0/38 (0%)    0/29 (0%)    1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          336          ---          ---       |   733 (T)      ---          ---          733 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.435N     P=0.203        (e)          (e)      |  P=0.601      P=0.439N     P=0.493N     P=0.732N   |
|INCIDENTAL TUMOR       |  P=0.531N     P=0.133        (e)          (e)      |  P=0.601      P=0.439N     P=0.493N     P=0.732N   |
|LOGISTIC REGRESSION    |  P=0.423N     P=0.204        (e)          (e)      |  P=0.601      P=0.439N     P=0.493N     P=0.732N   |
|COCHRAN-ARMITAGE       |  P=0.404N                                          |  P=0.595                                           |
|FISHER EXACT           |               P=0.244        (e)          (e)      |               P=0.500N     P=0.500N     P=0.752N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   7
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    2/59 (3%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    0/60 (0%)    0/60 (0%)    2/60 (3%)  |
|ADJUSTED (b)           |   3.5%         6.6%         0.0%         0.0%      |   3.6%         0.0%         0.0%         5.9%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/9 (0%)     0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    1/20 (5%)    0/21 (0%)    0/20 (0%)  |  1/28 (4%)    0/38 (0%)    0/29 (0%)    1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   446          336          ---          ---       |   733 (T)      ---          ---          719       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.096N     P=0.651      P=0.236N     P=0.240N   |  P=0.254      P=0.439N     P=0.493N     P=0.553    |
|INCIDENTAL TUMOR       |  P=0.128N     P=0.500      P=0.295N     P=0.220N   |  P=0.295      P=0.439N     P=0.493N     P=0.609    |
|LOGISTIC REGRESSION    |  P=0.111N     P=0.618      P=0.354N     P=0.289N   |  P=0.269      P=0.439N     P=0.493N     P=0.577    |
|COCHRAN-ARMITAGE       |  P=0.086N                                          |  P=0.246                                           |
|FISHER EXACT           |               P=0.684      P=0.248N     P=0.248N   |               P=0.500N     P=0.500N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  3/60 (5%)    2/60 (3%)    3/60 (5%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   8.5%         5.3%        10.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    0/20 (0%)    0/21 (0%)    0/20 (0%)  |  1/28 (4%)    2/38 (5%)    3/29 (10%)   0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   495          733 (T)      733 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.101N     P=0.388N     P=0.629N     P=0.100N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.110N     P=0.440N     P=0.631      P=0.107N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.094N     P=0.468N     P=0.622N     P=0.125N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.112N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.500N     P=0.660N     P=0.122N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   8
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/60 (0%)    1/60 (2%)    1/60 (2%)  | 27/60 (45%)  21/60 (35%)  27/60 (45%)   8/60 (13%) |
|ADJUSTED (b)           |   3.4%         0.0%         3.6%         4.0%      |  70.3%        47.3%        68.2%        23.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/29 (3%)    0/20 (0%)    0/21 (0%)    0/20 (0%)  | 17/28 (61%)  15/38 (39%)  17/29 (59%)   6/32 (19%) |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          707          708       |   475          400          641          645       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.492      P=0.574N     P=0.717      P=0.698    |  P<0.001N**   P=0.019N*    P=0.419N     P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.575      P=0.574N     P=0.734N     P=0.740N   |  P<0.001N**   P=0.062N     P=0.396N     P<0.001N** |
|LOGISTIC REGRESSION    |  P=0.520      P=0.574N     P=0.753      P=0.741    |  P<0.001N**   P=0.046N*    P=0.296N     P<0.001N** |
|COCHRAN-ARMITAGE       |  P=0.539                                           |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.500N     P=0.752N     P=0.752N   |               P=0.176N     P=0.573N     P<0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    0/60 (0%)    1/60 (2%)    1/60 (2%)  | 30/60 (50%)  23/60 (38%)  29/60 (48%)   8/60 (13%) |
|ADJUSTED (b)           |   3.4%         0.0%         3.6%         4.0%      |  74.4%        51.8%        73.5%        23.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/29 (3%)    0/20 (0%)    0/21 (0%)    0/20 (0%)  | 18/28 (64%)  17/38 (45%)  19/29 (66%)   6/32 (19%) |
|FIRST INCIDENCE (DAYS) |   732 (T)      ---          707          708       |   475          400          641          645       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.492      P=0.574N     P=0.717      P=0.698    |  P<0.001N**   P=0.011N*    P=0.344N     P<0.001N** |
|INCIDENTAL TUMOR       |  P=0.575      P=0.574N     P=0.734N     P=0.740N   |  P<0.001N**   P=0.033N*    P=0.334N     P<0.001N** |
|LOGISTIC REGRESSION    |  P=0.520      P=0.574N     P=0.753      P=0.741    |  P<0.001N**   P=0.029N*    P=0.216N     P<0.001N** |
|COCHRAN-ARMITAGE       |  P=0.539                                           |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.500N     P=0.752N     P=0.752N   |               P=0.135N     P=0.500N     P<0.001N** |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE   9
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   0.0%         6.7%         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%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    0/20 (0%)    0/21 (0%)    0/20 (0%)  |  0/28 (0%)    0/38 (0%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          627          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.432N     P=0.213        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.346N     P=0.386        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.408N     P=0.238        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.405N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/60 (17%)   5/60 (8%)    6/58 (10%)   4/57 (7%)  | 17/56 (30%)  18/60 (30%)  20/59 (34%)  12/60 (20%) |
|ADJUSTED (b)           |  30.1%        16.1%        24.4%        13.0%      |  51.4%        43.2%        50.0%        34.3%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   1/10 (10%)   0/10 (0%)    0/10 (0%)  |  1/10 (10%)   1/10 (10%)   1/9 (11%)    0/9 (0%)   |
|TERMINAL (d)           |  8/29 (28%)   1/20 (5%)    4/20 (20%)   0/20 (0%)  | 12/27 (44%)  15/38 (39%)  11/29 (38%)  10/32 (31%) |
|FIRST INCIDENCE (DAYS) |   449          455 (I)      526          594       |   456 (I)      456 (I)      427          631       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.162N     P=0.275N     P=0.406N     P=0.176N   |  P=0.107N     P=0.248N     P=0.475      P=0.077N   |
|INCIDENTAL TUMOR       |  P=0.107N     P=0.208N     P=0.436N     P=0.103N   |  P=0.056N     P=0.208N     P=0.427N     P=0.041N*  |
|LOGISTIC REGRESSION    |  P=0.106N     P=0.132N     P=0.224N     P=0.101N   |  P=0.050N*    P=0.304N     P=0.552N     P=0.038N*  |
|COCHRAN-ARMITAGE       |  P=0.098N                                          |  P=0.117N                                          |
|FISHER EXACT           |               P=0.135N     P=0.232N     P=0.092N   |               P=0.563N     P=0.418      P=0.142N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  10
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/60 (17%)   5/60 (8%)    6/58 (10%)   4/57 (7%)  | 18/56 (32%)  19/60 (32%)  20/59 (34%)  12/60 (20%) |
|ADJUSTED (b)           |  30.1%        16.1%        24.4%        13.0%      |  54.7%        44.6%        50.0%        34.3%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   1/10 (10%)   0/10 (0%)    0/10 (0%)  |  1/10 (10%)   1/10 (10%)   1/9 (11%)    0/9 (0%)   |
|TERMINAL (d)           |  8/29 (28%)   1/20 (5%)    4/20 (20%)   0/20 (0%)  | 13/27 (48%)  15/38 (39%)  11/29 (38%)  10/32 (31%) |
|FIRST INCIDENCE (DAYS) |   449          455 (I)      526          594       |   456 (I)      456 (I)      427          631       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.162N     P=0.275N     P=0.406N     P=0.176N   |  P=0.070N     P=0.233N     P=0.554      P=0.049N*  |
|INCIDENTAL TUMOR       |  P=0.107N     P=0.208N     P=0.436N     P=0.103N   |  P=0.029N*    P=0.176N     P=0.339N     P=0.024N*  |
|LOGISTIC REGRESSION    |  P=0.106N     P=0.132N     P=0.224N     P=0.101N   |  P=0.028N*    P=0.281N     P=0.455N     P=0.021N*  |
|COCHRAN-ARMITAGE       |  P=0.098N                                          |  P=0.077N                                          |
|FISHER EXACT           |               P=0.135N     P=0.232N     P=0.092N   |               P=0.557N     P=0.500      P=0.100N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal                                                       |
|     Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepithelioma                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    3/60 (5%)    4/60 (7%)    3/60 (5%)  |  1/60 (2%)    1/60 (2%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   6.9%        14.3%        17.2%        12.4%      |   3.6%         2.6%         1.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    1/9 (11%)    0/9 (0%)   |
|TERMINAL (d)           |  2/29 (7%)    2/20 (10%)   3/21 (14%)   2/20 (10%) |  1/28 (4%)    1/38 (3%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      729          706          594       |   733 (T)      733 (T)      456 (I)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.288      P=0.338      P=0.219      P=0.360    |  P=0.316N     P=0.692N     P=0.753      P=0.473N   |
|INCIDENTAL TUMOR       |  P=0.335      P=0.430      P=0.260      P=0.391    |  P=0.316N     P=0.692N     P=0.753      P=0.473N   |
|LOGISTIC REGRESSION    |  P=0.377      P=0.359      P=0.283      P=0.472    |  P=0.317N     P=0.692N     P=0.740      P=0.473N   |
|COCHRAN-ARMITAGE       |  P=0.421                                           |  P=0.312N                                          |
|FISHER EXACT           |               P=0.500      P=0.340      P=0.500    |               P=0.752N     P=0.752N     P=0.500N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  11
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/60 (8%)    2/60 (3%)    3/60 (5%)    1/60 (2%)  |  2/60 (3%)    1/60 (2%)    3/60 (5%)    1/60 (2%)  |
|ADJUSTED (b)           |  15.8%         8.4%        11.8%         3.0%      |   5.8%         2.6%         7.8%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  4/29 (14%)   1/20 (5%)    2/21 (10%)   0/20 (0%)  |  1/28 (4%)    1/38 (3%)    0/29 (0%)    1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   567          693          635          670       |   547          733 (T)      659          733 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.153N     P=0.336N     P=0.487N     P=0.173N   |  P=0.445N     P=0.422N     P=0.557      P=0.456N   |
|INCIDENTAL TUMOR       |  P=0.117N     P=0.249N     P=0.406N     P=0.124N   |  P=0.383N     P=0.629N     P=0.684N     P=0.560N   |
|LOGISTIC REGRESSION    |  P=0.103N     P=0.228N     P=0.353N     P=0.113N   |  P=0.449N     P=0.476N     P=0.523      P=0.476N   |
|COCHRAN-ARMITAGE       |  P=0.096N                                          |  P=0.474N                                          |
|FISHER EXACT           |               P=0.219N     P=0.359N     P=0.103N   |               P=0.500N     P=0.500      P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/60 (8%)    3/60 (5%)    3/60 (5%)    1/60 (2%)  |  3/60 (5%)    1/60 (2%)    4/60 (7%)    1/60 (2%)  |
|ADJUSTED (b)           |  15.8%        10.0%        11.8%         3.0%      |   7.4%         2.6%        10.7%         3.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  4/29 (14%)   1/20 (5%)    2/21 (10%)   0/20 (0%)  |  1/28 (4%)    1/38 (3%)    0/29 (0%)    1/32 (3%)  |
|FIRST INCIDENCE (DAYS) |   567          426          635          670       |   313          733 (T)      659          733 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.129N     P=0.489N     P=0.487N     P=0.173N   |  P=0.317N     P=0.250N     P=0.553      P=0.275N   |
|INCIDENTAL TUMOR       |  P=0.093N     P=0.461N     P=0.406N     P=0.124N   |  P=0.293N     P=0.629N     P=0.596N     P=0.560N   |
|LOGISTIC REGRESSION    |  P=0.083N     P=0.355N     P=0.353N     P=0.113N   |  P=0.350N     P=0.361N     P=0.471      P=0.358N   |
|COCHRAN-ARMITAGE       |  P=0.080N                                          |  P=0.344N                                          |
|FISHER EXACT           |               P=0.359N     P=0.359N     P=0.103N   |               P=0.309N     P=0.500      P=0.309N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  12
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    2/60 (3%)    2/60 (3%)    2/60 (3%)  |  0/60 (0%)    1/60 (2%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.4%         9.5%         9.5%         7.5%      |   0.0%         2.6%         1.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    1/9 (11%)    0/9 (0%)   |
|TERMINAL (d)           |  1/29 (3%)    1/20 (5%)    2/21 (10%)   1/20 (5%)  |  0/28 (0%)    1/38 (3%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      729          732 (T)      594       |   ---          733 (T)      456 (I)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.324      P=0.378      P=0.387      P=0.406    |  P=0.605N     P=0.561      P=0.479        (e)      |
|INCIDENTAL TUMOR       |  P=0.362      P=0.498      P=0.387      P=0.447    |  P=0.605N     P=0.561      P=0.479        (e)      |
|LOGISTIC REGRESSION    |  P=0.395      P=0.398      P=0.387      P=0.488    |  P=0.618N     P=0.561      P=0.422        (e)      |
|COCHRAN-ARMITAGE       |  P=0.423                                           |  P=0.595N                                          |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.500    |               P=0.500      P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    3/60 (5%)    3/60 (5%)    3/60 (5%)  |  1/60 (2%)    1/60 (2%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.4%        14.3%        14.3%        12.4%      |   3.6%         2.6%         1.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    1/9 (11%)    0/9 (0%)   |
|TERMINAL (d)           |  1/29 (3%)    2/20 (10%)   3/21 (14%)   2/20 (10%) |  1/28 (4%)    1/38 (3%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      729          732 (T)      594       |   733 (T)      733 (T)      456 (I)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.188      P=0.189      P=0.196      P=0.207    |  P=0.316N     P=0.692N     P=0.753      P=0.473N   |
|INCIDENTAL TUMOR       |  P=0.211      P=0.266      P=0.196      P=0.234    |  P=0.316N     P=0.692N     P=0.753      P=0.473N   |
|LOGISTIC REGRESSION    |  P=0.257      P=0.200      P=0.196      P=0.287    |  P=0.317N     P=0.692N     P=0.740      P=0.473N   |
|COCHRAN-ARMITAGE       |  P=0.293                                           |  P=0.312N                                          |
|FISHER EXACT           |               P=0.309      P=0.309      P=0.309    |               P=0.752N     P=0.752N     P=0.500N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  13
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    3/60 (5%)    2/60 (3%)    3/60 (5%)  |  1/60 (2%)    1/60 (2%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.4%        14.3%         9.5%        12.4%      |   3.6%         2.6%         1.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    1/9 (11%)    0/9 (0%)   |
|TERMINAL (d)           |  1/29 (3%)    2/20 (10%)   2/21 (10%)   2/20 (10%) |  1/28 (4%)    1/38 (3%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      729          732 (T)      594       |   733 (T)      733 (T)      456 (I)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.203      P=0.189      P=0.387      P=0.207    |  P=0.316N     P=0.692N     P=0.753      P=0.473N   |
|INCIDENTAL TUMOR       |  P=0.229      P=0.266      P=0.387      P=0.234    |  P=0.316N     P=0.692N     P=0.753      P=0.473N   |
|LOGISTIC REGRESSION    |  P=0.270      P=0.200      P=0.387      P=0.287    |  P=0.317N     P=0.692N     P=0.740      P=0.473N   |
|COCHRAN-ARMITAGE       |  P=0.303                                           |  P=0.312N                                          |
|FISHER EXACT           |               P=0.309      P=0.500      P=0.309    |               P=0.752N     P=0.752N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 53/60 (88%)  57/60 (95%)  56/60 (93%)  57/60 (95%) |                                                    |
|ADJUSTED (b)           |  98.1%       100.0%       100.0%       100.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  6/10 (60%)  10/10 (100%)  7/10 (70%)   9/10 (90%) |                                                    |
|TERMINAL (d)           | 28/29 (97%)  20/20 (100%) 21/21 (100%) 20/20 (100%)|                                                    |
|FIRST INCIDENCE (DAYS) |   334          426          455 (I)      455 (I)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.055      P=0.036 *    P=0.085      P=0.034 *  |                                                    |
|INCIDENTAL TUMOR       |  P=0.175      P=0.287      P=0.450      P=0.199    |                                                    |
|LOGISTIC REGRESSION    |  P=0.217      P=0.216      P=0.513      P=0.196    |                                                    |
|COCHRAN-ARMITAGE       |  P=0.164                                           |                                                    |
|FISHER EXACT           |               P=0.161      P=0.264      P=0.161    |                                                    |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  14
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    3/60 (5%)    2/60 (3%)    2/60 (3%)  |  4/60 (7%)    3/60 (5%)    5/60 (8%)    3/60 (5%)  |
|ADJUSTED (b)           |   9.7%        12.0%         9.5%         8.5%      |  12.6%         6.9%        16.1%         8.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/29 (7%)    1/20 (5%)    2/21 (10%)   1/20 (5%)  |  3/28 (11%)   1/38 (3%)    4/29 (14%)   2/32 (6%)  |
|FIRST INCIDENCE (DAYS) |   681          684          732 (T)      705       |   475          606          686          702       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.472N     P=0.543      P=0.619N     P=0.614N   |  P=0.444N     P=0.360N     P=0.531      P=0.430N   |
|INCIDENTAL TUMOR       |  P=0.390N     P=0.582N     P=0.562N     P=0.489N   |  P=0.445N     P=0.551N     P=0.472      P=0.448N   |
|LOGISTIC REGRESSION    |  P=0.406N     P=0.638      P=0.528N     P=0.542N   |  P=0.425N     P=0.461N     P=0.579      P=0.431N   |
|COCHRAN-ARMITAGE       |  P=0.372N                                          |  P=0.482N                                          |
|FISHER EXACT           |               P=0.660N     P=0.500N     P=0.500N   |               P=0.500N     P=0.500      P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    2/60 (3%)    4/60 (7%)    3/60 (5%)  |  2/60 (3%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   6.9%        10.0%        17.3%         9.9%      |   6.8%         2.6%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/29 (7%)    2/20 (10%)   3/21 (14%)   0/20 (0%)  |  1/28 (4%)    1/38 (3%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      732 (T)      707          659       |   712          733 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.260      P=0.555      P=0.216      P=0.411    |  P=0.094N     P=0.397N     P=0.236N     P=0.203N   |
|INCIDENTAL TUMOR       |  P=0.321      P=0.555      P=0.260      P=0.603    |  P=0.072N     P=0.412N     P=0.148N     P=0.154N   |
|LOGISTIC REGRESSION    |  P=0.318      P=0.555      P=0.281      P=0.472    |  P=0.084N     P=0.403N     P=0.206N     P=0.191N   |
|COCHRAN-ARMITAGE       |  P=0.357                                           |  P=0.101N                                          |
|FISHER EXACT           |               P=0.691N     P=0.340      P=0.500    |               P=0.500N     P=0.248N     P=0.248N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  15
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/60 (8%)    5/60 (8%)    5/60 (8%)    5/60 (8%)  |  6/60 (10%)   4/60 (7%)    5/60 (8%)    3/60 (5%)  |
|ADJUSTED (b)           |  16.4%        21.3%        21.9%        17.6%      |  18.9%         9.4%        16.1%         8.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  4/29 (14%)   3/20 (15%)   4/21 (19%)   1/20 (5%)  |  4/28 (14%)   2/38 (5%)    4/29 (14%)   2/32 (6%)  |
|FIRST INCIDENCE (DAYS) |   681          684          707          659       |   475          606          686          702       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.416      P=0.437      P=0.455      P=0.483    |  P=0.198N     P=0.219N     P=0.470N     P=0.183N   |
|INCIDENTAL TUMOR       |  P=0.532      P=0.609      P=0.545      P=0.555N   |  P=0.182N     P=0.358N     P=0.470N     P=0.167N   |
|LOGISTIC REGRESSION    |  P=0.511      P=0.568      P=0.584      P=0.585    |  P=0.176N     P=0.295N     P=0.406N     P=0.174N   |
|COCHRAN-ARMITAGE       |  P=0.563                                           |  P=0.228N                                          |
|FISHER EXACT           |               P=0.628N     P=0.628N     P=0.628N   |               P=0.372N     P=0.500N     P=0.245N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    0/60 (0%)    2/60 (3%)    2/60 (3%)  |
|ADJUSTED (b)           |   3.4%         2.7%         0.0%         0.0%      |   2.1%         0.0%         5.6%         6.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/29 (3%)    0/20 (0%)    0/21 (0%)    0/20 (0%)  |  0/28 (0%)    0/38 (0%)    1/29 (3%)    2/32 (6%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      651          ---          ---       |   475          ---          643          733 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.268N     P=0.720      P=0.564N     P=0.574N   |  P=0.258      P=0.496N     P=0.536      P=0.531    |
|INCIDENTAL TUMOR       |  P=0.229N     P=0.728N     P=0.564N     P=0.574N   |  P=0.185      P=0.581N     P=0.283      P=0.453    |
|LOGISTIC REGRESSION    |  P=0.240N     P=0.760      P=0.564N     P=0.574N   |  P=0.250      P=0.580N     P=0.479      P=0.502    |
|COCHRAN-ARMITAGE       |  P=0.236N                                          |  P=0.246                                           |
|FISHER EXACT           |               P=0.752N     P=0.500N     P=0.500N   |               P=0.500N     P=0.500      P=0.500    |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  16
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/60 (2%)    7/60 (12%)   7/60 (12%)   3/60 (5%)  |
|ADJUSTED (b)           |                                                    |   3.6%        16.4%        20.6%         6.9%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    1/10 (10%)   1/9 (11%)    0/9 (0%)   |
|TERMINAL (d)           |                                                    |  1/28 (4%)    5/38 (13%)   5/29 (17%)   0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   733 (T)      456 (I)      456 (I)      473       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.490      P=0.069      P=0.038 *    P=0.368    |
|INCIDENTAL TUMOR       |                                                    |  P=0.482      P=0.057      P=0.046 *    P=0.375    |
|LOGISTIC REGRESSION    |                                                    |  P=0.487      P=0.041 *    P=0.045 *    P=0.304    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.467                                           |
|FISHER EXACT           |                                                    |               P=0.031 *    P=0.031 *    P=0.309    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/60 (2%)    7/60 (12%)   8/60 (13%)   3/60 (5%)  |
|ADJUSTED (b)           |                                                    |   3.6%        16.4%        22.7%         6.9%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    1/10 (10%)   1/9 (11%)    0/9 (0%)   |
|TERMINAL (d)           |                                                    |  1/28 (4%)    5/38 (13%)   5/29 (17%)   0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   733 (T)      456 (I)      456 (I)      473       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.481      P=0.069      P=0.024 *    P=0.368    |
|INCIDENTAL TUMOR       |                                                    |  P=0.491      P=0.057      P=0.035 *    P=0.375    |
|LOGISTIC REGRESSION    |                                                    |  P=0.474      P=0.041 *    P=0.026 *    P=0.304    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.452                                           |
|FISHER EXACT           |                                                    |               P=0.031 *    P=0.016 *    P=0.309    |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  17
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    1/60 (2%)    3/60 (5%)    1/60 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         2.4%         7.1%         2.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/29 (0%)    0/20 (0%)    0/21 (0%)    0/20 (0%)  |  0/28 (0%)    0/38 (0%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          705          606          718       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.401      P=0.567      P=0.169      P=0.543    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.495      P=0.531      P=0.190      P=0.638    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.366      P=0.537      P=0.124      P=0.541    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.351                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.500      P=0.122      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 33/60 (55%)  27/60 (45%)  37/60 (62%)  37/60 (62%) | 15/60 (25%)  16/60 (27%)  18/60 (30%)  12/60 (20%) |
|ADJUSTED (b)           |  73.1%        64.1%        79.2%        81.4%      |  36.2%        34.3%        52.1%        27.3%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    1/10 (10%)   0/10 (0%)  |  1/10 (10%)   0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 17/29 (59%)   7/20 (35%)  12/21 (57%)  12/20 (60%) |  5/28 (18%)   8/38 (21%)  13/29 (45%)   2/32 (6%)  |
|FIRST INCIDENCE (DAYS) |   455 (I)      404          455 (I)      355       |   432          479          635          617       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.055      P=0.495N     P=0.146      P=0.094    |  P=0.220N     P=0.369N     P=0.440      P=0.197N   |
|INCIDENTAL TUMOR       |  P=0.180      P=0.020N*    P=0.512N     P=0.499    |  P=0.164N     P=0.353      P=0.343      P=0.216N   |
|LOGISTIC REGRESSION    |  P=0.178      P=0.038N*    P=0.494N     P=0.448    |  P=0.228N     P=0.311      P=0.441      P=0.434N   |
|COCHRAN-ARMITAGE       |  P=0.118                                           |  P=0.282N                                          |
|FISHER EXACT           |               P=0.181N     P=0.289      P=0.289    |               P=0.500      P=0.342      P=0.331N   |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  18
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma: Benign, Malignant, NOS                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    2/60 (3%)    3/60 (5%)    3/60 (5%)  |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   3.4%         5.7%         9.9%         7.7%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/29 (3%)    0/20 (0%)    0/21 (0%)    0/20 (0%)  |  0/28 (0%)    0/38 (0%)    0/29 (0%)    0/32 (0%)  |
|FIRST INCIDENCE (DAYS) |   732 (T)      574          455 (I)      484       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.205      P=0.459      P=0.245      P=0.274    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.301      P=0.601      P=0.387      P=0.371    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.228      P=0.501      P=0.311      P=0.306    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.228                                           |    (e)                                             |
|FISHER EXACT           |               P=0.500      P=0.309      P=0.309    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 56/60 (93%)  57/60 (95%)  57/60 (95%)  57/60 (95%) | 39/60 (65%)  42/60 (70%)  44/60 (73%)  27/60 (45%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  90.5%        83.8%        91.3%        65.1%      |
|INTERIM SACRIFICE 1 (c)|  7/10 (70%)  10/10 (100%)  7/10 (70%)   9/10 (90%) |  1/10 (10%)   2/10 (20%)   3/9 (33%)    0/9 (0%)   |
|TERMINAL (d)           | 29/29 (100%) 20/20 (100%) 21/21 (100%) 20/20 (100%)| 24/28 (86%)  30/38 (79%)  25/29 (86%)  18/32 (56%) |
|FIRST INCIDENCE (DAYS) |   334          426          455 (I)      455 (I)   |   456 (I)      400          427          473       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.100      P=0.080      P=0.135      P=0.075    |  P=0.007N**   P=0.129N     P=0.437      P=0.004N** |
|INCIDENTAL TUMOR       |  P=0.514      P=0.643      P=0.683      P=0.599    |  P<0.001N**   P=0.529N     P=0.339      P=0.001N** |
|LOGISTIC REGRESSION    |  P=0.576N     P=0.665      P=0.467N     P=0.669    |  P<0.001N**   P=0.490N     P=0.497      P=0.001N** |
|COCHRAN-ARMITAGE       |  P=0.443                                           |  P=0.007N**                                        |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.500    |               P=0.348      P=0.215      P=0.022N*  |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  19
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        400  PPM     800 PPM      1600      |   0 PPM        400 PPM      800 PPM      1600      |
|                       |                                          PPM       |                                          PPM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 37/60 (62%)  33/60 (55%)  41/60 (68%)  41/60 (68%) | 28/60 (47%)  20/60 (33%)  28/60 (47%)  17/60 (28%) |
|ADJUSTED (b)           |  80.2%        74.3%        82.9%        83.5%      |  62.1%        41.6%        66.0%        36.7%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    2/10 (20%)   0/10 (0%)  |  1/10 (10%)   0/10 (0%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 20/29 (69%)  10/20 (50%)  13/21 (62%)  12/20 (60%) | 12/28 (43%)  10/38 (26%)  15/29 (52%)   4/32 (13%) |
|FIRST INCIDENCE (DAYS) |   203          336          455 (I)      355       |   313          479          365          444       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.064      P=0.442      P=0.132      P=0.088    |  P=0.047N*    P=0.020N*    P=0.416N     P=0.016N*  |
|INCIDENTAL TUMOR       |  P=0.196      P=0.108N     P=0.525      P=0.490    |  P=0.010N*    P=0.171N     P=0.405N     P=0.009N** |
|LOGISTIC REGRESSION    |  P=0.124      P=0.256N     P=0.353      P=0.266    |  P=0.038N*    P=0.066N     P=0.455N     P=0.022N*  |
|COCHRAN-ARMITAGE       |  P=0.139                                           |  P=0.056N                                          |
|FISHER EXACT           |               P=0.289N     P=0.283      P=0.283    |               P=0.096N     P=0.573N     P=0.029N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 57/60 (95%)  60/60 (100%) 59/60 (98%)  59/60 (98%) | 48/60 (80%)  46/60 (77%)  50/60 (83%)  37/60 (62%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  95.9%        88.4%        96.1%        75.4%      |
|INTERIM SACRIFICE 1 (c)|  7/10 (70%)  10/10 (100%)  9/10 (90%)   9/10 (90%) |  2/10 (20%)   2/10 (20%)   3/9 (33%)    0/9 (0%)   |
|TERMINAL (d)           | 29/29 (100%) 20/20 (100%) 21/21 (100%) 20/20 (100%)| 26/28 (93%)  32/38 (84%)  27/29 (93%)  20/32 (63%) |
|FIRST INCIDENCE (DAYS) |   203          336          455 (I)      355       |   313          400          365          444       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.094      P=0.053      P=0.108      P=0.063    |  P=0.026N*    P=0.023N*    P=0.461N     P=0.010N** |
|INCIDENTAL TUMOR       |  P=0.288      P=0.111      P=0.293      P=0.293    |  P<0.001N**   P=0.338N     P=0.484      P=0.002N** |
|LOGISTIC REGRESSION    |  P=0.391      P=0.160      P=0.497      P=0.381    |  P=0.001N**   P=0.163N     P=0.529N     P=0.002N** |
|COCHRAN-ARMITAGE       |  P=0.296                                           |  P=0.014N*                                         |
|FISHER EXACT           |               P=0.122      P=0.309      P=0.309    |               P=0.412N     P=0.407      P=0.022N*  |
|=================================================================================================================================|
         DATE: 04/02/96                     EXPERIMENT: 05068 TEST: 09                                                 PAGE  20
                                 STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS
                                                                           

 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   455
          Female interim sacrifices(days): 456
 (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).