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TDMS Study 05068-10 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Microbiological Assoc.                                     CODEINE                                        DATE: 04/03/96       
EXPERIMENT: 05068 TEST: 10                                                                                     TIME: 01:16:25       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-75178                              ROUTE: DOSED FEED                                              NTP C#: 61541B       
PATHOLOGIST: MISSING                                                                                           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: 04/03/96       
EXPERIMENT: 05068 TEST: 10                                                                                     TIME: 01:16:25       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-75178                              ROUTE: DOSED FEED                                              NTP C#: 61541B       
PATHOLOGIST: MISSING                                                                                           CAS: 76-57-3         




                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                                    

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

                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Microbiological Assoc.                                     CODEINE                                        DATE: 04/03/96       
EXPERIMENT: 05068 TEST: 10                                                                                     TIME: 01:16:25       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-75178                              ROUTE: DOSED FEED                                              NTP C#: 61541B       
PATHOLOGIST: MISSING                                                                                           CAS: 76-57-3         




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

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

                                                           MALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------

              Liver                         Hepatocellular Adenoma
                                            Hepatocellular Carcinoma or Hepatocellular Adenoma
                                            Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
              All Organs                    Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated
                                             Cell Type
                                            Benign Tumors
                                            Malignant Tumors
                                            Malignant and Benign Tumors

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

                                                           FEMALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------

              Liver                         Hepatocellular Adenoma
                                            Hepatocellular Carcinoma or Hepatocellular Adenoma
                                            Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
              All Organs                    Benign Tumors
                                            Malignant Tumors

              ====================================================================================================
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   1
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    3/60 (5%)    5/60 (8%)    3/60 (5%)  |  1/60 (2%)    3/60 (5%)    1/60 (2%)    2/59 (3%)  |
|ADJUSTED (b)           |   7.3%         7.9%        11.1%         7.0%      |   2.8%         8.3%         2.3%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/41 (7%)    3/38 (8%)    5/45 (11%)   3/43 (7%)  |  1/36 (3%)    3/36 (8%)    1/43 (2%)    2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   731 (T)      731 (T)      731 (T)      731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.563N     P=0.628      P=0.408      P=0.641N   |  P=0.524      P=0.305      P=0.722N     P=0.490    |
|INCIDENTAL TUMOR       |  P=0.563N     P=0.628      P=0.408      P=0.641N   |  P=0.524      P=0.305      P=0.722N     P=0.490    |
|LOGISTIC REGRESSION    |  P=0.563N     P=0.628      P=0.408      P=0.641N   |  P=0.524      P=0.305      P=0.722N     P=0.490    |
|COCHRAN-ARMITAGE       |  P=0.537                                           |  P=0.519                                           |
|FISHER EXACT           |               P=0.660N     P=0.359      P=0.660N   |               P=0.309      P=0.752N     P=0.494    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    3/60 (5%)    5/60 (8%)    3/60 (5%)  |  1/60 (2%)    4/60 (7%)    1/60 (2%)    2/59 (3%)  |
|ADJUSTED (b)           |   7.3%         7.9%        11.1%         7.0%      |   2.8%        10.5%         2.3%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  3/41 (7%)    3/38 (8%)    5/45 (11%)   3/43 (7%)  |  1/36 (3%)    3/36 (8%)    1/43 (2%)    2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   731 (T)      616          731 (T)      731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.563N     P=0.628      P=0.408      P=0.641N   |  P=0.597N     P=0.184      P=0.722N     P=0.490    |
|INCIDENTAL TUMOR       |  P=0.563N     P=0.628      P=0.408      P=0.641N   |  P=0.594      P=0.164      P=0.722N     P=0.490    |
|LOGISTIC REGRESSION    |  P=0.563N     P=0.628      P=0.408      P=0.641N   |  P=0.574N     P=0.171      P=0.722N     P=0.490    |
|COCHRAN-ARMITAGE       |  P=0.537                                           |  P=0.589                                           |
|FISHER EXACT           |               P=0.660N     P=0.359      P=0.660N   |               P=0.182      P=0.752N     P=0.494    |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   2
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    2/60 (3%)    1/60 (2%)    0/59 (0%)  |
|ADJUSTED (b)           |   4.5%         2.6%         0.0%         0.0%      |   2.1%         5.6%         2.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/41 (2%)    1/38 (3%)    0/45 (0%)    0/43 (0%)  |  0/36 (0%)    2/36 (6%)    1/43 (2%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   546          729 (T)      ---          ---       |   497          731 (T)      731 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.096N     P=0.518N     P=0.225N     P=0.237N   |  P=0.245N     P=0.493      P=0.741N     P=0.504N   |
|INCIDENTAL TUMOR       |  P=0.112N     P=0.564N     P=0.481N     P=0.235N   |  P=0.293N     P=0.533      P=0.535      P=0.581N   |
|LOGISTIC REGRESSION    |  P=0.100N     P=0.502N     P=0.241N     P=0.238N   |  P=0.247N     P=0.496      P=0.756      P=0.493N   |
|COCHRAN-ARMITAGE       |  P=0.101N                                          |  P=0.251N                                          |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |               P=0.500      P=0.752N     P=0.504N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 26/60 (43%)  26/60 (43%)  18/60 (30%)  11/60 (18%) | 14/60 (23%)  11/60 (18%)  13/60 (22%)   5/59 (8%)  |
|ADJUSTED (b)           |  55.8%        58.5%        37.7%        23.4%      |  34.3%        26.6%        30.2%        14.3%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   1/10 (10%)   2/10 (20%)   1/10 (10%) |  2/10 (20%)   1/9 (11%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 21/41 (51%)  20/38 (53%)  16/45 (36%)   8/43 (19%) | 11/36 (31%)   7/36 (19%)  13/43 (30%)   5/35 (14%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      456 (I)      456 (I)   |   457 (I)      457 (I)      731 (T)      731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001N**   P=0.458      P=0.046N*    P=0.002N** |  P=0.022N*    P=0.343N     P=0.324N     P=0.026N*  |
|INCIDENTAL TUMOR       |  P<0.001N**   P=0.541      P=0.061N     P=0.001N** |  P=0.023N*    P=0.359N     P=0.407N     P=0.029N*  |
|LOGISTIC REGRESSION    |  P<0.001N**   P=0.559      P=0.069N     P=0.002N** |  P=0.018N*    P=0.347N     P=0.411N     P=0.021N*  |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.027N*                                         |
|FISHER EXACT           |               P=0.573N     P=0.092N     P=0.003N** |               P=0.327N     P=0.500N     P=0.024N*  |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   3
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/60 (22%)   8/60 (13%)  13/60 (22%)   8/60 (13%) |  5/60 (8%)    7/60 (12%)   6/60 (10%)   4/59 (7%)  |
|ADJUSTED (b)           |  28.2%        17.8%        27.1%        17.0%      |  12.5%        17.2%        14.0%        10.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    1/9 (11%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/41 (20%)   3/38 (8%)   10/45 (22%)   5/43 (12%) |  3/36 (8%)    4/36 (11%)   6/43 (14%)   2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   497          396          635          456 (I)   |   565          457 (I)      731 (T)      720       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.183N     P=0.214N     P=0.480N     P=0.153N   |  P=0.345N     P=0.371      P=0.610      P=0.501N   |
|INCIDENTAL TUMOR       |  P=0.329N     P=0.074N     P=0.514      P=0.204N   |  P=0.305N     P=0.317      P=0.447      P=0.463N   |
|LOGISTIC REGRESSION    |  P=0.298N     P=0.155N     P=0.493      P=0.242N   |  P=0.334N     P=0.367      P=0.554      P=0.496N   |
|COCHRAN-ARMITAGE       |  P=0.228N                                          |  P=0.364N                                          |
|FISHER EXACT           |               P=0.168N     P=0.588N     P=0.168N   |               P=0.381      P=0.500      P=0.511N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 13/60 (22%)   9/60 (15%)  13/60 (22%)   8/60 (13%) |  5/60 (8%)    7/60 (12%)   6/60 (10%)   4/59 (7%)  |
|ADJUSTED (b)           |  28.2%        19.7%        27.1%        17.0%      |  12.5%        17.2%        14.0%        10.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    1/9 (11%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  8/41 (20%)   3/38 (8%)   10/45 (22%)   5/43 (12%) |  3/36 (8%)    4/36 (11%)   6/43 (14%)   2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   497          396          635          456 (I)   |   565          457 (I)      731 (T)      720       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.163N     P=0.290N     P=0.480N     P=0.153N   |  P=0.345N     P=0.371      P=0.610      P=0.501N   |
|INCIDENTAL TUMOR       |  P=0.339N     P=0.105N     P=0.514      P=0.204N   |  P=0.305N     P=0.317      P=0.447      P=0.463N   |
|LOGISTIC REGRESSION    |  P=0.289N     P=0.218N     P=0.493      P=0.242N   |  P=0.334N     P=0.367      P=0.554      P=0.496N   |
|COCHRAN-ARMITAGE       |  P=0.205N                                          |  P=0.364N                                          |
|FISHER EXACT           |               P=0.240N     P=0.588N     P=0.168N   |               P=0.381      P=0.500      P=0.511N   |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   4
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/60 (53%)  30/60 (50%)  25/60 (42%)  18/60 (30%) | 18/60 (30%)  17/60 (28%)  15/60 (25%)   8/59 (14%) |
|ADJUSTED (b)           |  64.9%        63.3%        49.7%        36.3%      |  42.3%        39.6%        34.9%        21.4%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   1/10 (10%)   2/10 (20%)   2/10 (20%) |  2/10 (20%)   2/9 (22%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 24/41 (59%)  21/38 (55%)  20/45 (44%)  12/43 (28%) | 13/36 (36%)  11/36 (31%)  15/43 (35%)   6/35 (17%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      396          456 (I)      456 (I)   |   457 (I)      457 (I)      731 (T)      720       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002N**   P=0.550N     P=0.073N     P=0.008N** |  P=0.013N*    P=0.522N     P=0.176N     P=0.029N*  |
|INCIDENTAL TUMOR       |  P=0.003N**   P=0.379N     P=0.112N     P=0.006N** |  P=0.011N*    P=0.566N     P=0.318N     P=0.026N*  |
|LOGISTIC REGRESSION    |  P=0.002N**   P=0.443N     P=0.095N     P=0.007N** |  P=0.010N**   P=0.530N     P=0.260N     P=0.021N*  |
|COCHRAN-ARMITAGE       |  P=0.003N**                                        |  P=0.016N*                                         |
|FISHER EXACT           |               P=0.428N     P=0.136N     P=0.008N** |               P=0.500N     P=0.342N     P=0.025N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 32/60 (53%)  31/60 (52%)  25/60 (42%)  18/60 (30%) | 18/60 (30%)  17/60 (28%)  15/60 (25%)   8/59 (14%) |
|ADJUSTED (b)           |  64.9%        64.1%        49.7%        36.3%      |  42.3%        39.6%        34.9%        21.4%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   1/10 (10%)   2/10 (20%)   2/10 (20%) |  2/10 (20%)   2/9 (22%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 24/41 (59%)  21/38 (55%)  20/45 (44%)  12/43 (28%) | 13/36 (36%)  11/36 (31%)  15/43 (35%)   6/35 (17%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      396          456 (I)      456 (I)   |   457 (I)      457 (I)      731 (T)      720       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.002N**   P=0.516      P=0.073N     P=0.008N** |  P=0.013N*    P=0.522N     P=0.176N     P=0.029N*  |
|INCIDENTAL TUMOR       |  P=0.004N**   P=0.434N     P=0.112N     P=0.006N** |  P=0.011N*    P=0.566N     P=0.318N     P=0.026N*  |
|LOGISTIC REGRESSION    |  P=0.003N**   P=0.519N     P=0.095N     P=0.007N** |  P=0.010N**   P=0.530N     P=0.260N     P=0.021N*  |
|COCHRAN-ARMITAGE       |  P=0.003N**                                        |  P=0.016N*                                         |
|FISHER EXACT           |               P=0.500N     P=0.136N     P=0.008N** |               P=0.500N     P=0.342N     P=0.025N*  |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   5
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/60 (27%)   8/60 (13%)  14/60 (23%)   9/60 (15%) |  3/60 (5%)    3/60 (5%)    6/60 (10%)   4/59 (7%)  |
|ADJUSTED (b)           |  37.7%        20.1%        30.4%        19.1%      |   6.1%         7.3%        13.5%        10.4%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    1/10 (10%) |  2/10 (20%)   1/9 (11%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 15/41 (37%)   7/38 (18%)  13/45 (29%)   7/43 (16%) |  1/36 (3%)    2/36 (6%)    5/43 (12%)   2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      474          727          401       |   457 (I)      457 (I)      724          711       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.105N     P=0.073N     P=0.304N     P=0.069N   |  P=0.359      P=0.639      P=0.309      P=0.485    |
|INCIDENTAL TUMOR       |  P=0.105N     P=0.080N     P=0.293N     P=0.069N   |  P=0.402      P=0.639      P=0.281      P=0.529    |
|LOGISTIC REGRESSION    |  P=0.130N     P=0.054N     P=0.309N     P=0.081N   |  P=0.365      P=0.650N     P=0.253      P=0.491    |
|COCHRAN-ARMITAGE       |  P=0.155N                                          |  P=0.353                                           |
|FISHER EXACT           |               P=0.054N     P=0.417N     P=0.088N   |               P=0.660N     P=0.245      P=0.491    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    2/60 (3%)    2/60 (3%)    2/60 (3%)  |  1/60 (2%)    1/60 (2%)    1/60 (2%)    0/59 (0%)  |
|ADJUSTED (b)           |   2.4%         4.7%         4.4%         4.7%      |   2.8%         2.8%         2.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/41 (2%)    1/38 (3%)    2/45 (4%)    2/43 (5%)  |  1/36 (3%)    1/36 (3%)    1/43 (2%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      474          729 (T)      729 (T)   |   731 (T)      731 (T)      731 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.452      P=0.482      P=0.533      P=0.517    |  P=0.308N     P=0.762      P=0.722N     P=0.506N   |
|INCIDENTAL TUMOR       |  P=0.453      P=0.436      P=0.533      P=0.517    |  P=0.308N     P=0.762      P=0.722N     P=0.506N   |
|LOGISTIC REGRESSION    |  P=0.430      P=0.501      P=0.533      P=0.517    |  P=0.308N     P=0.762      P=0.722N     P=0.506N   |
|COCHRAN-ARMITAGE       |  P=0.423                                           |  P=0.315N                                          |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.500    |               P=0.752N     P=0.752N     P=0.504N   |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   6
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/60 (27%)   9/60 (15%)  16/60 (27%)  11/60 (18%) |  4/60 (7%)    4/60 (7%)    7/60 (12%)   4/59 (7%)  |
|ADJUSTED (b)           |  37.7%        22.7%        34.8%        23.6%      |   8.8%        10.0%        15.8%        10.4%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    1/10 (10%) |  2/10 (20%)   1/9 (11%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 15/41 (37%)   8/38 (21%)  15/45 (33%)   9/43 (21%) |  2/36 (6%)    3/36 (8%)    6/43 (14%)   2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   456 (I)      474          727          401       |   457 (I)      457 (I)      724          711       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.217N     P=0.117N     P=0.461N     P=0.155N   |  P=0.513      P=0.622      P=0.344      P=0.626    |
|INCIDENTAL TUMOR       |  P=0.217N     P=0.126N     P=0.449N     P=0.155N   |  P=0.553      P=0.622      P=0.318      P=0.619N   |
|LOGISTIC REGRESSION    |  P=0.260N     P=0.088N     P=0.468N     P=0.176N   |  P=0.525      P=0.641N     P=0.283      P=0.636    |
|COCHRAN-ARMITAGE       |  P=0.298N                                          |  P=0.505                                           |
|FISHER EXACT           |               P=0.088N     P=0.582N     P=0.191N   |               P=0.641N     P=0.264      P=0.632    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    0/60 (0%)    2/60 (3%)    2/59 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         4.4%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/41 (0%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  0/36 (0%)    0/36 (0%)    1/43 (2%)    2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          643          731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.083        (e)        P=0.277      P=0.232    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.090        (e)        P=0.118      P=0.232    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.089        (e)        P=0.247      P=0.232    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.084                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)        P=0.248      P=0.244    |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   7
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/58 (3%)    3/60 (5%)    0/59 (0%)    2/59 (3%)  |
|ADJUSTED (b)           |                                                    |   5.6%         8.3%         0.0%         5.7%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/9 (0%)     0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  2/36 (6%)    3/36 (8%)    0/43 (0%)    2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   731 (T)      731 (T)      ---          731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.476N     P=0.500      P=0.200N     P=0.685    |
|INCIDENTAL TUMOR       |                                                    |  P=0.476N     P=0.500      P=0.200N     P=0.685    |
|LOGISTIC REGRESSION    |                                                    |  P=0.476N     P=0.500      P=0.200N     P=0.685    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.471N                                          |
|FISHER EXACT           |                                                    |               P=0.516      P=0.244N     P=0.684N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/56 (0%)    0/59 (0%)    0/58 (0%)    0/55 (0%)  | 11/58 (19%)   9/56 (16%)  17/58 (29%)  10/55 (18%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  29.7%        25.9%        39.4%        30.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/37 (0%)    0/45 (0%)    0/42 (0%)  | 10/36 (28%)   8/33 (24%)  16/42 (38%)  10/33 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   722          512          703          731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.473      P=0.482N     P=0.264      P=0.586N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.480      P=0.455N     P=0.231      P=0.571N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.532N     P=0.503N     P=0.270      P=0.528N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.463                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.437N     P=0.139      P=0.554N   |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   8
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/56 (0%)    0/59 (0%)    0/58 (0%)    0/55 (0%)  | 11/58 (19%)   9/56 (16%)  18/58 (31%)  10/55 (18%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  29.7%        25.9%        41.7%        30.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/37 (0%)    0/45 (0%)    0/42 (0%)  | 10/36 (28%)   8/33 (24%)  17/42 (40%)  10/33 (30%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   722          512          703          731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.460      P=0.482N     P=0.202      P=0.586N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.468      P=0.455N     P=0.174      P=0.571N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.542N     P=0.503N     P=0.207      P=0.528N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.451                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.437N     P=0.099      P=0.554N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Intermedia                                                                                                 |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/56 (0%)    0/59 (0%)    0/58 (0%)    0/55 (0%)  |  1/58 (2%)    1/56 (2%)    3/58 (5%)    1/55 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   2.3%         2.7%         7.1%         3.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/37 (0%)    0/45 (0%)    0/42 (0%)  |  0/36 (0%)    0/33 (0%)    3/42 (7%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   570          677          731 (T)      731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.556      P=0.752      P=0.357      P=0.753    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.550      P=0.703      P=0.234      P=0.719    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.553      P=0.762      P=0.320      P=0.751    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.540                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.743      P=0.309      P=0.739    |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE   9
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Intermedia                                                                                                 |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/56 (2%)    0/59 (0%)    0/58 (0%)    0/55 (0%)  |  1/58 (2%)    1/56 (2%)    3/58 (5%)    1/55 (2%)  |
|ADJUSTED (b)           |   2.1%         0.0%         0.0%         0.0%      |   2.3%         2.7%         7.1%         3.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/9 (0%)   |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/39 (0%)    0/37 (0%)    0/45 (0%)    0/42 (0%)  |  0/36 (0%)    0/33 (0%)    3/42 (7%)    1/33 (3%)  |
|FIRST INCIDENCE (DAYS) |   546          ---          ---          ---       |   570          677          731 (T)      731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.307N     P=0.500N     P=0.492N     P=0.504N   |  P=0.556      P=0.752      P=0.357      P=0.753    |
|INCIDENTAL TUMOR       |  P=0.399N     P=0.581N       (e)        P=0.581N   |  P=0.550      P=0.703      P=0.234      P=0.719    |
|LOGISTIC REGRESSION    |  P=0.313N     P=0.455N     P=0.471N     P=0.517N   |  P=0.553      P=0.762      P=0.320      P=0.751    |
|COCHRAN-ARMITAGE       |  P=0.308N                                          |  P=0.540                                           |
|FISHER EXACT           |               P=0.487N     P=0.491N     P=0.505N   |               P=0.743      P=0.309      P=0.739    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    4/60 (7%)    1/60 (2%)    2/59 (3%)  |
|ADJUSTED (b)           |   3.9%         2.2%         0.0%         0.0%      |   2.8%        10.6%         2.2%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/41 (0%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  1/36 (3%)    3/36 (8%)    0/43 (0%)    2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   227          566          ---          ---       |   731 (T)      647          727          731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.099N     P=0.505N     P=0.230N     P=0.237N   |  P=0.595N     P=0.180      P=0.715N     P=0.490    |
|INCIDENTAL TUMOR       |  P=0.221N     P=0.378N     P=0.353N     P=0.500N   |  P=0.550N     P=0.168      P=0.756      P=0.490    |
|LOGISTIC REGRESSION    |  P=0.085N     P=0.431N     P=0.182N     P=0.168N   |  P=0.572N     P=0.170      P=0.722N     P=0.490    |
|COCHRAN-ARMITAGE       |  P=0.101N                                          |  P=0.589                                           |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |               P=0.182      P=0.752N     P=0.494    |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE  10
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         5.2%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/41 (0%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  0/36 (0%)    1/36 (3%)    0/43 (0%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          647          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.399N     P=0.237        (e)          (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.365N     P=0.215        (e)          (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.401N     P=0.232        (e)          (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.408N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.248        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    4/60 (7%)    1/60 (2%)    2/59 (3%)  |
|ADJUSTED (b)           |   3.9%         2.2%         0.0%         0.0%      |   2.8%        10.6%         2.2%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/41 (0%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  1/36 (3%)    3/36 (8%)    0/43 (0%)    2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   227          566          ---          ---       |   731 (T)      647          727          731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.099N     P=0.505N     P=0.230N     P=0.237N   |  P=0.595N     P=0.180      P=0.715N     P=0.490    |
|INCIDENTAL TUMOR       |  P=0.221N     P=0.378N     P=0.353N     P=0.500N   |  P=0.550N     P=0.168      P=0.756      P=0.490    |
|LOGISTIC REGRESSION    |  P=0.085N     P=0.431N     P=0.182N     P=0.168N   |  P=0.572N     P=0.170      P=0.722N     P=0.490    |
|COCHRAN-ARMITAGE       |  P=0.101N                                          |  P=0.589                                           |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |               P=0.182      P=0.752N     P=0.494    |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE  11
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    2/60 (3%)    1/60 (2%)    2/59 (3%)  |
|ADJUSTED (b)           |   3.9%         2.2%         0.0%         0.0%      |   2.8%         5.6%         2.2%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/41 (0%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  1/36 (3%)    2/36 (6%)    0/43 (0%)    2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   227          566          ---          ---       |   731 (T)      731 (T)      727          731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.099N     P=0.505N     P=0.230N     P=0.237N   |  P=0.444      P=0.500      P=0.715N     P=0.490    |
|INCIDENTAL TUMOR       |  P=0.221N     P=0.378N     P=0.353N     P=0.500N   |  P=0.470      P=0.500      P=0.756      P=0.490    |
|LOGISTIC REGRESSION    |  P=0.085N     P=0.431N     P=0.182N     P=0.168N   |  P=0.471      P=0.500      P=0.722N     P=0.490    |
|COCHRAN-ARMITAGE       |  P=0.101N                                          |  P=0.438                                           |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |               P=0.500      P=0.752N     P=0.494    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    2/60 (3%)    2/60 (3%)    2/60 (3%)  |  1/58 (2%)    4/60 (7%)    3/60 (5%)    2/59 (3%)  |
|ADJUSTED (b)           |   2.4%         5.3%         4.4%         4.7%      |   1.7%        11.1%         7.0%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  1/10 (10%)   0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  1/41 (2%)    2/38 (5%)    2/45 (4%)    2/43 (5%)  |  0/34 (0%)    4/36 (11%)   3/43 (7%)    2/35 (6%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      729 (T)      729 (T)      729 (T)   |   457 (I)      731 (T)      731 (T)      731 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.456      P=0.473      P=0.533      P=0.517    |  P=0.557      P=0.189      P=0.361      P=0.495    |
|INCIDENTAL TUMOR       |  P=0.456      P=0.473      P=0.533      P=0.517    |  P=0.557      P=0.189      P=0.361      P=0.495    |
|LOGISTIC REGRESSION    |  P=0.456      P=0.473      P=0.533      P=0.517    |  P=0.577      P=0.186      P=0.322      P=0.506    |
|COCHRAN-ARMITAGE       |  P=0.428                                           |  P=0.548                                           |
|FISHER EXACT           |               P=0.506      P=0.506      P=0.506    |               P=0.193      P=0.322      P=0.506    |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE  12
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  4/60 (7%)    0/60 (0%)    2/60 (3%)    0/59 (0%)  |
|ADJUSTED (b)           |                                                    |  10.6%         0.0%         4.7%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |                                                    |  3/36 (8%)    0/36 (0%)    2/43 (5%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   651          ---          731 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.057N     P=0.066N     P=0.263N     P=0.067N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.054N     P=0.072N     P=0.288N     P=0.056N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.054N     P=0.066N     P=0.281N     P=0.059N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.064N                                          |
|FISHER EXACT           |                                                    |               P=0.059N     P=0.340N     P=0.061N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    1/60 (2%)    2/60 (3%)    1/59 (2%)  |
|ADJUSTED (b)           |   4.9%         2.1%         0.0%         0.0%      |   2.6%         2.6%         4.4%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/41 (5%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  0/36 (0%)    0/36 (0%)    1/43 (2%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      559          ---          ---       |   713          664          703          506       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.095N     P=0.515N     P=0.218N     P=0.228N   |  P=0.610      P=0.754      P=0.567      P=0.757N   |
|INCIDENTAL TUMOR       |  P=0.139N     P=0.459N     P=0.218N     P=0.228N   |  P=0.608N     P=0.723      P=0.468      P=0.757    |
|LOGISTIC REGRESSION    |  P=0.100N     P=0.502N     P=0.218N     P=0.228N   |  P=0.524      P=0.757      P=0.428      P=0.759    |
|COCHRAN-ARMITAGE       |  P=0.101N                                          |  P=0.585                                           |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |               P=0.752N     P=0.500      P=0.748    |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE  13
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/60 (3%)    1/60 (2%)    0/60 (0%)    0/60 (0%)  |  1/60 (2%)    2/60 (3%)    3/60 (5%)    1/59 (2%)  |
|ADJUSTED (b)           |   4.9%         2.1%         0.0%         0.0%      |   2.6%         5.3%         6.7%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  2/41 (5%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  0/36 (0%)    1/36 (3%)    2/43 (5%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   729 (T)      559          ---          ---       |   713          664          703          506       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.095N     P=0.515N     P=0.218N     P=0.228N   |  P=0.562N     P=0.494      P=0.377      P=0.757N   |
|INCIDENTAL TUMOR       |  P=0.139N     P=0.459N     P=0.218N     P=0.228N   |  P=0.543N     P=0.446      P=0.293      P=0.757    |
|LOGISTIC REGRESSION    |  P=0.100N     P=0.502N     P=0.218N     P=0.228N   |  P=0.574N     P=0.491      P=0.352      P=0.759    |
|COCHRAN-ARMITAGE       |  P=0.101N                                          |  P=0.584N                                          |
|FISHER EXACT           |               P=0.500N     P=0.248N     P=0.248N   |               P=0.500      P=0.309      P=0.748    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    2/60 (3%)    0/60 (0%)    2/60 (3%)  |  2/60 (3%)    2/60 (3%)    0/60 (0%)    1/59 (2%)  |
|ADJUSTED (b)           |   0.0%         5.0%         0.0%         4.7%      |   4.8%         4.9%         0.0%         2.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/41 (0%)    1/38 (3%)    0/45 (0%)    2/43 (5%)  |  1/36 (3%)    0/36 (0%)    0/43 (0%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          716          ---          729 (T)   |   530          625          ---          598       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.269      P=0.231        (e)        P=0.249    |  P=0.282N     P=0.685      P=0.218N     P=0.495N   |
|INCIDENTAL TUMOR       |  P=0.271      P=0.304        (e)        P=0.249    |  P=0.325N     P=0.673      P=0.465N     P=0.550N   |
|LOGISTIC REGRESSION    |  P=0.263      P=0.234        (e)        P=0.249    |  P=0.423N     P=0.680      P=0.242N     P=0.506N   |
|COCHRAN-ARMITAGE       |  P=0.248                                           |  P=0.301N                                          |
|FISHER EXACT           |               P=0.248        (e)        P=0.248    |               P=0.691N     P=0.248N     P=0.506N   |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE  14
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated                                               |
|     Cell Type                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/60 (12%)   1/60 (2%)    1/60 (2%)    0/60 (0%)  |  8/60 (13%)   5/60 (8%)    6/60 (10%)   8/59 (14%) |
|ADJUSTED (b)           |  15.1%         2.6%         2.2%         0.0%      |  18.8%        12.1%        12.8%        19.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  1/10 (10%)   0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  4/41 (10%)   1/38 (3%)    1/45 (2%)    0/43 (0%)  |  4/36 (11%)   3/36 (8%)    2/43 (5%)    4/35 (11%) |
|FIRST INCIDENCE (DAYS) |   450          729 (T)      729 (T)      ---       |   457 (I)      348          703          556       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.003N**   P=0.043N*    P=0.028N*    P=0.010N** |  P=0.477      P=0.294N     P=0.281N     P=0.599    |
|INCIDENTAL TUMOR       |  P=0.007N**   P=0.029N*    P=0.089N     P=0.032N*  |  P=0.521      P=0.278N     P=0.586N     P=0.592N   |
|LOGISTIC REGRESSION    |  P=0.003N**   P=0.034N*    P=0.034N*    P=0.010N** |  P=0.461      P=0.283N     P=0.356N     P=0.535    |
|COCHRAN-ARMITAGE       |  P=0.003N**                                        |  P=0.445                                           |
|FISHER EXACT           |               P=0.031N*    P=0.031N*    P=0.006N** |               P=0.279N     P=0.389N     P=0.591    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         4.5%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/41 (0%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  0/36 (0%)    1/36 (3%)    0/43 (0%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          359          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.406N     P=0.238        (e)          (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.422N     P=0.314        (e)          (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.410N     P=0.251        (e)          (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.408N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.248        (e)          (e)      |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE  15
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/60 (0%)    0/60 (0%)    0/60 (0%)    0/60 (0%)  |  0/60 (0%)    2/60 (3%)    0/60 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         4.5%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/9 (0%)     0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           |  0/41 (0%)    0/38 (0%)    0/45 (0%)    0/43 (0%)  |  0/36 (0%)    1/36 (3%)    0/43 (0%)    0/35 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          359          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.406N     P=0.238        (e)          (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.422N     P=0.314        (e)          (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.410N     P=0.251        (e)          (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.408N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.248        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 37/60 (62%)  33/60 (55%)  32/60 (53%)  24/60 (40%) | 30/60 (50%)  27/60 (45%)  33/60 (55%)  19/59 (32%) |
|ADJUSTED (b)           |  78.4%        74.7%        65.0%        48.1%      |  67.1%        62.2%        73.3%        51.1%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   1/10 (10%)   2/10 (20%)   3/10 (30%) |  4/10 (40%)   2/9 (22%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 31/41 (76%)  27/38 (71%)  28/45 (62%)  18/43 (42%) | 22/36 (61%)  20/36 (56%)  31/43 (72%)  17/35 (49%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      456 (I)      401       |   457 (I)      457 (I)      703          711       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.003N**   P=0.441N     P=0.093N     P=0.009N** |  P=0.027N*    P=0.389N     P=0.428N     P=0.037N*  |
|INCIDENTAL TUMOR       |  P=0.004N**   P=0.363N     P=0.176N     P=0.005N** |  P=0.019N*    P=0.415N     P=0.536      P=0.028N*  |
|LOGISTIC REGRESSION    |  P=0.005N**   P=0.290N     P=0.137N     P=0.011N*  |  P=0.015N*    P=0.402N     P=0.528      P=0.022N*  |
|COCHRAN-ARMITAGE       |  P=0.010N*                                         |  P=0.041N*                                         |
|FISHER EXACT           |               P=0.289N     P=0.230N     P=0.014N*  |               P=0.357N     P=0.357      P=0.037N*  |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE  16
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- CODEINE

                                                 TERMINAL SACRIFICE AT 105 WEEKS

|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 PPM        750 PPM      1500 PPM     3000 PPM  |   0 PPM        750 PPM      1500 PPM     3000 PPM  |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 20/60 (33%)  15/60 (25%)  15/60 (25%)  11/60 (18%) | 16/60 (27%)  25/60 (42%)  17/60 (28%)  19/59 (32%) |
|ADJUSTED (b)           |  39.6%        31.1%        31.2%        23.6%      |  35.4%        52.4%        34.5%        41.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  1/10 (10%)   1/9 (11%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 11/41 (27%)   6/38 (16%)  12/45 (27%)   8/43 (19%) |  8/36 (22%)  14/36 (39%)  11/43 (26%)   9/35 (26%) |
|FIRST INCIDENCE (DAYS) |   227          396          635          456 (I)   |   457 (I)      348          329          397       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.038N*    P=0.280N     P=0.153N     P=0.049N*  |  P=0.519N     P=0.079      P=0.459N     P=0.357    |
|INCIDENTAL TUMOR       |  P=0.124N     P=0.077N     P=0.421N     P=0.079N   |  P=0.507N     P=0.041 *    P=0.231      P=0.333    |
|LOGISTIC REGRESSION    |  P=0.044N*    P=0.208N     P=0.194N     P=0.047N*  |  P=0.524      P=0.055      P=0.546      P=0.241    |
|COCHRAN-ARMITAGE       |  P=0.047N*                                         |  P=0.501                                           |
|FISHER EXACT           |               P=0.211N     P=0.211N     P=0.047N*  |               P=0.062      P=0.500      P=0.322    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 44/60 (73%)  40/60 (67%)  38/60 (63%)  32/60 (53%) | 38/60 (63%)  39/60 (65%)  38/60 (63%)  31/59 (53%) |
|ADJUSTED (b)           |  82.8%        81.4%        75.8%        61.0%      |  75.5%        77.6%        77.5%        67.1%      |
|INTERIM SACRIFICE 1 (c)|  3/10 (30%)   1/10 (10%)   2/10 (20%)   4/10 (40%) |  4/10 (40%)   3/9 (33%)    0/9 (0%)     0/9 (0%)   |
|TERMINAL (d)           | 32/41 (78%)  29/38 (76%)  33/45 (73%)  23/43 (53%) | 24/36 (67%)  25/36 (69%)  32/43 (74%)  20/35 (57%) |
|FIRST INCIDENCE (DAYS) |   227          396          456 (I)      401       |   457 (I)      348          329          397       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.007N**   P=0.460N     P=0.067N     P=0.021N*  |  P=0.107N     P=0.462      P=0.211N     P=0.197N   |
|INCIDENTAL TUMOR       |  P=0.015N*    P=0.223N     P=0.207N     P=0.022N*  |  P=0.056N     P=0.440      P=0.431      P=0.122N   |
|LOGISTIC REGRESSION    |  P=0.008N**   P=0.286N     P=0.102N     P=0.017N*  |  P=0.063N     P=0.446      P=0.444N     P=0.132N   |
|COCHRAN-ARMITAGE       |  P=0.013N*                                         |  P=0.102N                                          |
|FISHER EXACT           |               P=0.275N     P=0.163N     P=0.018N*  |               P=0.500      P=0.575N     P=0.157N   |
|=================================================================================================================================|
         DATE: 04/03/96                     EXPERIMENT: 05068 TEST: 10                                                 PAGE  17
                                   STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 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):   456
          Female interim sacrifices(days): 457
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.

  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.