05217-ch-mouse-p03
05217-ch1-mouse-p04
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08
LAB: Southern Research Inst                               T-BUTYLHYDROQUINONE                                  DATE: 04/04/96
EXPERIMENT: 05217 TEST: 05                                                                                     TIME: 09:19:12
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1
CONT: NO1-ES-85219                              ROUTE: DOSED FEED                                              NTP C#: C62157
PATHOLOGIST: D.R. FARNELL                                                                                      CAS: 1948-33-0
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE
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
Islets, Pancreatic
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF THE STUDY OF T-BUTYLHYDROQUINONE
====================================================================================================
MALE MICE
ORGAN                               MORPHOLOGY
-------                             ------------
Liver                         Hepatocellular Adenoma
Hepatocellular Carcinoma or Hepatocellular Adenoma
Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
Spleen                        Hemangiosarcoma
All Organs                    Hemangiosarcoma
Hemangiosarcoma or Hemangioma
Benign Tumors
FEMALE MICE
Harderian Gland               Adenoma
Carcinoma or Adenoma
All Organs                    Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated
Malignant and Benign Tumors
DATE: 04/04/96                     EXPERIMENT: 05217 TEST: 05                                                 PAGE   1
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- T-BUTYLHYDROQUINONE
MALE TERMINAL SACRIFICE AT 104 WEEKS
FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|DOSE                   |   UNTREATD     0.125%       0.25%        0.5%      |   UNTREATD     0.125%       0.25%        0.5%      |
|                       |   CONTROL                                          |   CONTROL                                          |
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/60 (2%)    4/60 (7%)    1/59 (2%)    2/60 (3%)  |  0/60 (0%)    0/59 (0%)    0/59 (0%)    0/60 (0%)  |
|ADJUSTED (b)           |   2.6%         8.7%         2.7%         4.8%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     0/9 (0%)   |  0/9 (0%)     0/8 (0%)     0/9 (0%)     0/6 (0%)   |
|TERMINAL (d)           |  1/39 (3%)    4/46 (9%)    1/37 (3%)    2/42 (5%)  |  0/38 (0%)    0/35 (0%)    0/40 (0%)    0/43 (0%)  |
|FIRST INCIDENCE (DAYS) |   727 (T)      727 (T)      727 (T)      727 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|LIFE TABLE             |  P=0.592N     P=0.233      P=0.750      P=0.526    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.592N     P=0.233      P=0.750      P=0.526    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.592N     P=0.233      P=0.750      P=0.526    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.595                                           |    (e)                                             |
|FISHER EXACT           |               P=0.182      P=0.748      P=0.500    |                 (e)          (e)          (e)      |
|Harderian Gland                                                                                                                  |
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|OVERALL (a)            |  3/60 (5%)    8/60 (13%)   4/60 (7%)    3/60 (5%)  |  0/60 (0%)    0/60 (0%)    6/60 (10%)   1/60 (2%)  |
|ADJUSTED (b)           |   7.7%        17.4%        10.5%         7.0%      |   0.0%         0.0%        15.0%         2.3%      |
|TERMINAL (d)           |  3/39 (8%)    8/46 (17%)   4/38 (11%)   2/42 (5%)  |  0/38 (0%)    0/35 (0%)    6/40 (15%)   1/43 (2%)  |
|FIRST INCIDENCE (DAYS) |   727 (T)      727 (T)      727 (T)      688       |   ---          ---          734 (T)      734 (T)   |
|LIFE TABLE             |  P=0.331N     P=0.159      P=0.486      P=0.631N   |  P=0.294        (e)        P=0.020 *    P=0.525    |
|INCIDENTAL TUMOR       |  P=0.357N     P=0.159      P=0.486      P=0.600    |  P=0.294        (e)        P=0.020 *    P=0.525    |
|LOGISTIC REGRESSION    |  P=0.351N     P=0.159      P=0.486      P=0.660N   |  P=0.294        (e)        P=0.020 *    P=0.525    |
|COCHRAN-ARMITAGE       |  P=0.339N                                          |  P=0.238                                           |
|FISHER EXACT           |               P=0.102      P=0.500      P=0.660N   |                 (e)        P=0.014 *    P=0.500    |
|     Carcinoma                                                                                                                   |
|FIRST INCIDENCE (DAYS) |   ---          ---          727 (T)      ---       |   ---          734 (T)      ---          ---       |
|LIFE TABLE             |  P=0.598        (e)        P=0.233        (e)      |  P=0.542N     P=0.484        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.598        (e)        P=0.233        (e)      |  P=0.542N     P=0.484        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.598        (e)        P=0.233        (e)      |  P=0.542N     P=0.484        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.595                                           |  P=0.567N                                          |
|FISHER EXACT           |                 (e)        P=0.248        (e)      |               P=0.500        (e)          (e)      |
|     Carcinoma or Adenoma                                                                                                        |
|OVERALL (a)            |  3/60 (5%)    8/60 (13%)   6/60 (10%)   3/60 (5%)  |  0/60 (0%)    1/60 (2%)    6/60 (10%)   1/60 (2%)  |
|FIRST INCIDENCE (DAYS) |   727 (T)      727 (T)      727 (T)      688       |   ---          734 (T)      734 (T)      734 (T)   |
|LIFE TABLE             |  P=0.367N     P=0.159      P=0.228      P=0.631N   |  P=0.379      P=0.484      P=0.020 *    P=0.525    |
|INCIDENTAL TUMOR       |  P=0.392N     P=0.159      P=0.228      P=0.600    |  P=0.379      P=0.484      P=0.020 *    P=0.525    |
|LOGISTIC REGRESSION    |  P=0.389N     P=0.159      P=0.228      P=0.660N   |  P=0.379      P=0.484      P=0.020 *    P=0.525    |
|FISHER EXACT           |               P=0.102      P=0.245      P=0.660N   |               P=0.500      P=0.014 *    P=0.500    |
|Intestine Small: Jejunum                                                                                                         |
|FIRST INCIDENCE (DAYS) |   ---          727 (T)      654          ---       |   ---          ---          ---          ---       |
|LIFE TABLE             |  P=0.632N     P=0.533      P=0.123        (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.580      P=0.533      P=0.120        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.629      P=0.533      P=0.118        (e)      |    (e)          (e)          (e)          (e)      |
|FISHER EXACT           |               P=0.500      P=0.122        (e)      |                 (e)          (e)          (e)      |
|Intestine Small: Site Unspecified                                                                                                |
|FIRST INCIDENCE (DAYS) |   727 (T)      727 (T)      654          ---       |   ---          ---          ---          ---       |
|LIFE TABLE             |  P=0.407N     P=0.724N     P=0.304      P=0.485N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.459N     P=0.724N     P=0.300      P=0.485N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.415N     P=0.724N     P=0.298      P=0.485N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.409N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.752N     P=0.309      P=0.500N   |                 (e)          (e)          (e)      |
|Islets, Pancreatic                                                                                                               |
|FIRST INCIDENCE (DAYS) |   727 (T)      710          ---          727 (T)   |   667          ---          734 (T)      ---       |
|LIFE TABLE             |  P=0.368      P=0.727N     P=0.505N     P=0.526    |  P=0.376N     P=0.505N     P=0.749N     P=0.473N   |
|INCIDENTAL TUMOR       |  P=0.308      P=0.647      P=0.505N     P=0.526    |  P=0.385N     P=0.388N     P=0.730N     P=0.455N   |
|LOGISTIC REGRESSION    |  P=0.359      P=0.749N     P=0.505N     P=0.526    |  P=0.396N     P=0.501N     P=0.760      P=0.500N   |
|FISHER EXACT           |               P=0.752N     P=0.500N     P=0.500    |               P=0.500N     P=0.739      P=0.500N   |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|FIRST INCIDENCE (DAYS) |   595          727 (T)      727 (T)      589       |   461          ---          ---          734 (T)   |
|LIFE TABLE             |  P=0.471N     P=0.262N     P=0.317N     P=0.478N   |  P=0.610      P=0.500N     P=0.504N     P=0.747N   |
|INCIDENTAL TUMOR       |  P=0.330N     P=0.264N     P=0.278N     P=0.294N   |  P=0.654      P=0.227N     P=0.500N     P=0.630N   |
|LOGISTIC REGRESSION    |  P=0.479N     P=0.298N     P=0.310N     P=0.501N   |  P=0.601      P=0.478N     P=0.467N     P=0.758N   |
|FISHER EXACT           |               P=0.309N     P=0.309N     P=0.500N   |               P=0.500N     P=0.500N     P=0.752N   |
|     Hepatocellular Adenoma                                                                                                      |
|OVERALL (a)            | 29/60 (48%)  23/60 (38%)  23/60 (38%)  14/60 (23%) |  9/60 (15%)  20/60 (33%)  17/60 (28%)   5/60 (8%)  |
|ADJUSTED (b)           |  61.2%        48.7%        53.8%        31.7%      |  22.7%        51.0%        38.1%        11.6%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   1/10 (10%)   1/9 (11%)    0/9 (0%)   |  0/9 (0%)     0/8 (0%)     1/9 (11%)    0/6 (0%)   |
|TERMINAL (d)           | 21/39 (54%)  22/46 (48%)  19/38 (50%)  12/42 (29%) |  8/38 (21%)  16/35 (46%)  13/40 (33%)   5/43 (12%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      409          630       |   582          598          457 (I)      734 (T)   |
|LIFE TABLE             |  P=0.003N**   P=0.055N     P=0.221N     P=0.003N** |  P=0.026N*    P=0.008 **   P=0.079      P=0.135N   |
|INCIDENTAL TUMOR       |  P=0.004N**   P=0.140N     P=0.167N     P=0.004N** |  P=0.044N*    P=0.010 **   P=0.061      P=0.183N   |
|LOGISTIC REGRESSION    |  P=0.003N**   P=0.128N     P=0.189N     P=0.003N** |  P=0.031N*    P=0.011 *    P=0.068      P=0.140N   |
|COCHRAN-ARMITAGE       |  P=0.004N**                                        |  P=0.064N                                          |
|FISHER EXACT           |               P=0.179N     P=0.179N     P=0.004N** |               P=0.016 *    P=0.060      P=0.197N   |
|     Hepatocellular Carcinoma                                                                                                    |
|OVERALL (a)            |  8/60 (13%)  11/60 (18%)  12/60 (20%)   9/60 (15%) |  8/60 (13%)   9/60 (15%)   8/60 (13%)   5/60 (8%)  |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/9 (11%)  |  0/9 (0%)     1/8 (13%)    0/9 (0%)     0/6 (0%)   |
|TERMINAL (d)           |  6/39 (15%)   9/46 (20%)   6/38 (16%)   5/42 (12%) |  4/38 (11%)   4/35 (11%)   4/40 (10%)   5/43 (12%) |
|FIRST INCIDENCE (DAYS) |   619          619          409          456 (I)   |   461          457 (I)      548          734 (T)   |
|LIFE TABLE             |  P=0.495      P=0.437      P=0.224      P=0.532    |  P=0.142N     P=0.459      P=0.561N     P=0.216N   |
|INCIDENTAL TUMOR       |  P=0.476N     P=0.358      P=0.314      P=0.571    |  P=0.272N     P=0.574      P=0.589      P=0.304N   |
|LOGISTIC REGRESSION    |  P=0.529      P=0.342      P=0.228      P=0.496    |  P=0.336N     P=0.502      P=0.485      P=0.259N   |
|FISHER EXACT           |               P=0.309      P=0.232      P=0.500    |               P=0.500      P=0.605N     P=0.279N   |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|LIFE TABLE             |  P=0.495      P=0.437      P=0.224      P=0.532    |  P=0.150N     P=0.459      P=0.543      P=0.216N   |
|FISHER EXACT           |               P=0.309      P=0.232      P=0.500    |               P=0.500      P=0.500      P=0.279N   |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|OVERALL (a)            | 32/60 (53%)  29/60 (48%)  30/60 (50%)  18/60 (30%) | 17/60 (28%)  29/60 (48%)  24/60 (40%)  10/60 (17%) |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   1/10 (10%)   1/9 (11%)    1/9 (11%)  |  0/9 (0%)     1/8 (13%)    1/9 (11%)    0/6 (0%)   |
|TERMINAL (d)           | 23/39 (59%)  26/46 (57%)  22/38 (58%)  14/42 (33%) | 12/38 (32%)  20/35 (57%)  16/40 (40%)  10/43 (23%) |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      409          456 (I)   |   461          457 (I)      457 (I)      734 (T)   |
|LIFE TABLE             |  P=0.008N**   P=0.133N     P=0.489N     P=0.007N** |  P=0.007N**   P=0.014 *    P=0.185      P=0.050N   |
|INCIDENTAL TUMOR       |  P=0.003N**   P=0.311N     P=0.366N     P=0.008N** |  P=0.021N*    P=0.017 *    P=0.112      P=0.094N   |
|COCHRAN-ARMITAGE       |  P=0.006N**                                        |  P=0.021N*                                         |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|OVERALL (a)            | 12/60 (20%)  11/58 (19%)  11/60 (18%)  10/60 (17%) |  4/60 (7%)    2/60 (3%)    4/60 (7%)    3/60 (5%)  |
|ADJUSTED (b)           |  28.1%        23.3%        24.7%        21.4%      |   9.5%         5.3%        10.0%         7.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    1/10 (10%)   2/9 (22%)    1/9 (11%)  |  1/9 (11%)    0/8 (0%)     0/9 (0%)     0/6 (0%)   |
|TERMINAL (d)           |  9/39 (23%)   9/44 (20%)   7/38 (18%)   7/42 (17%) |  3/38 (8%)    1/35 (3%)    4/40 (10%)   3/43 (7%)  |
|FIRST INCIDENCE (DAYS) |   647          456 (I)      456 (I)      456 (I)   |   457 (I)      706          734 (T)      734 (T)   |
|LIFE TABLE             |  P=0.365N     P=0.393N     P=0.536N     P=0.364N   |  P=0.451N     P=0.374N     P=0.618N     P=0.473N   |
|INCIDENTAL TUMOR       |  P=0.312N     P=0.568N     P=0.510N     P=0.428N   |  P=0.456N     P=0.331N     P=0.618N     P=0.473N   |
|LOGISTIC REGRESSION    |  P=0.365N     P=0.508N     P=0.511N     P=0.410N   |  P=0.476N     P=0.341N     P=0.631N     P=0.484N   |
|COCHRAN-ARMITAGE       |  P=0.356N                                          |  P=0.519N                                          |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|OVERALL (a)            |  3/60 (5%)    5/58 (9%)    3/60 (5%)    6/60 (10%) |  2/60 (3%)    0/60 (0%)    1/60 (2%)    0/60 (0%)  |
|ADJUSTED (b)           |   7.0%        11.0%         7.2%        13.3%      |   5.3%         0.0%         2.5%         0.0%      |
|TERMINAL (d)           |  1/39 (3%)    4/44 (9%)    1/38 (3%)    4/42 (10%) |  2/38 (5%)    0/35 (0%)    1/40 (3%)    0/43 (0%)  |
|FIRST INCIDENCE (DAYS) |   651          654          666          595       |   734 (T)      ---          734 (T)      ---       |
|LIFE TABLE             |  P=0.242      P=0.418      P=0.648      P=0.266    |  P=0.166N     P=0.257N     P=0.482N     P=0.212N   |
|INCIDENTAL TUMOR       |  P=0.191      P=0.158      P=0.666      P=0.226    |  P=0.166N     P=0.257N     P=0.482N     P=0.212N   |
|LOGISTIC REGRESSION    |  P=0.234      P=0.355      P=0.657      P=0.242    |  P=0.166N     P=0.257N     P=0.482N     P=0.212N   |
|FISHER EXACT           |               P=0.340      P=0.660N     P=0.245    |               P=0.248N     P=0.500N     P=0.248N   |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|OVERALL (a)            | 15/60 (25%)  16/58 (28%)  13/60 (22%)  15/60 (25%) |  6/60 (10%)   2/60 (3%)    5/60 (8%)    3/60 (5%)  |
|ADJUSTED (b)           |  33.7%        33.5%        28.8%        31.2%      |  14.6%         5.3%        12.5%         7.0%      |
|TERMINAL (d)           | 10/39 (26%)  13/44 (30%)   8/38 (21%)  10/42 (24%) |  5/38 (13%)   1/35 (3%)    5/40 (13%)   3/43 (7%)  |
|INCIDENTAL TUMOR       |  P=0.444N     P=0.312      P=0.426N     P=0.562    |  P=0.238N     P=0.139N     P=0.467N     P=0.212N   |
|LOGISTIC REGRESSION    |  P=0.454N     P=0.364      P=0.427N     P=0.582    |  P=0.252N     P=0.139N     P=0.477N     P=0.221N   |
|FISHER EXACT           |               P=0.456      P=0.415N     P=0.583N   |               P=0.136N     P=0.500N     P=0.245N   |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|OVERALL (a)            |                                                    |  2/59 (3%)    2/57 (4%)    4/56 (7%)    2/56 (4%)  |
|ADJUSTED (b)           |                                                    |   5.4%         5.3%         9.5%         5.1%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/9 (0%)     0/8 (0%)     1/9 (11%)    0/6 (0%)   |
|TERMINAL (d)           |                                                    |  2/37 (5%)    1/34 (3%)    3/38 (8%)    2/39 (5%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   734 (T)      654          457 (I)      734 (T)   |
|LIFE TABLE             |                                                    |  P=0.566      P=0.671      P=0.348      P=0.676N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.567      P=0.691      P=0.348      P=0.676N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.542      P=0.676      P=0.319      P=0.676N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.521                                           |
|FISHER EXACT           |                                                    |               P=0.678      P=0.315      P=0.671    |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|OVERALL (a)            |  1/55 (2%)    0/52 (0%)    0/53 (0%)    0/57 (0%)  |  5/58 (9%)    5/52 (10%)   5/55 (9%)    4/55 (7%)  |
|ADJUSTED (b)           |   2.5%         0.0%         0.0%         0.0%      |  12.3%        16.1%        13.2%        10.5%      |
|INTERIM SACRIFICE 1 (c)|  0/9 (0%)     0/10 (0%)    0/8 (0%)     0/8 (0%)   |  0/9 (0%)     0/8 (0%)     0/9 (0%)     0/6 (0%)   |
|TERMINAL (d)           |  0/36 (0%)    0/39 (0%)    0/33 (0%)    0/40 (0%)  |  3/36 (8%)    5/31 (16%)   5/38 (13%)   4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   723          ---          ---          ---       |   567          734 (T)      734 (T)      734 (T)   |
|LIFE TABLE             |  P=0.306N     P=0.472N     P=0.505N     P=0.490N   |  P=0.351N     P=0.550      P=0.600N     P=0.465N   |
|INCIDENTAL TUMOR       |  P=0.382N     P=0.872N     P=0.473N     P=0.748N   |  P=0.467N     P=0.481      P=0.514      P=0.602    |
|LOGISTIC REGRESSION    |  P=0.302N     P=0.501N     P=0.514N     P=0.489N   |  P=0.369N     P=0.549      P=0.627      P=0.507N   |
|FISHER EXACT           |               P=0.514N     P=0.509N     P=0.491N   |               P=0.558      P=0.595      P=0.534N   |
DATE: 04/04/96                     EXPERIMENT: 05217 TEST: 05                                                 PAGE  10
|FIRST INCIDENCE (DAYS) |   723          ---          ---          ---       |   567          598          734 (T)      734 (T)   |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   734 (T)      623          734 (T)      703       |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.315N     P=0.675      P=0.676N     P=0.450N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.405N     P=0.641      P=0.676N     P=0.446N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.340N     P=0.690      P=0.676N     P=0.463N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.373N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.691N     P=0.691N     P=0.500N   |
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 |
|FIRST INCIDENCE (DAYS) |   619          727 (T)      727 (T)      ---       |   ---          ---          ---          ---       |
|LIFE TABLE             |  P=0.154N     P=0.457N     P=0.508N     P=0.236N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.105N     P=0.462N     P=0.460N     P=0.123N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.155N     P=0.494N     P=0.504N     P=0.238N   |    (e)          (e)          (e)          (e)      |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.248N   |                 (e)          (e)          (e)      |
|     Sarcoma                                                                                                                     |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   734 (T)      623          734 (T)      ---       |
|Spleen                                                                                                                           |
|FIRST INCIDENCE (DAYS) |   647          727 (T)      ---          ---       |   ---          ---          723          ---       |
|LIFE TABLE             |  P=0.020N*    P=0.144N     P=0.068N     P=0.060N   |  P=0.713        (e)        P=0.515        (e)      |
|INCIDENTAL TUMOR       |  P=0.024N*    P=0.207N     P=0.067N     P=0.092N   |  P=0.705        (e)        P=0.545        (e)      |
|LOGISTIC REGRESSION    |  P=0.020N*    P=0.166N     P=0.066N     P=0.063N   |  P=0.708        (e)        P=0.509        (e)      |
|COCHRAN-ARMITAGE       |  P=0.020N*                                         |  P=0.694                                           |
|FISHER EXACT           |               P=0.182N     P=0.059N     P=0.059N   |                 (e)        P=0.496        (e)      |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|FIRST INCIDENCE (DAYS) |   ---          727 (T)      727 (T)      688       |   734 (T)      494          ---          734 (T)   |
|LIFE TABLE             |  P=0.155      P=0.533      P=0.495      P=0.251    |  P=0.405      P=0.751      P=0.490N     P=0.543    |
|INCIDENTAL TUMOR       |  P=0.114      P=0.533      P=0.495      P=0.111    |  P=0.436      P=0.635N     P=0.490N     P=0.543    |
|LOGISTIC REGRESSION    |  P=0.148      P=0.533      P=0.495      P=0.238    |  P=0.369      P=0.759N     P=0.490N     P=0.543    |
|COCHRAN-ARMITAGE       |  P=0.153                                           |  P=0.367                                           |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.248    |               P=0.752N     P=0.500N     P=0.500    |
|     Squamous Cell Papilloma                                                                                                     |
|FIRST INCIDENCE (DAYS) |   ---          727 (T)      727 (T)      688       |   734 (T)      ---          ---          734 (T)   |
|LIFE TABLE             |  P=0.155      P=0.533      P=0.495      P=0.251    |  P=0.284      P=0.516N     P=0.490N     P=0.543    |
|Thyroid Gland: Follicular Cell                                                                                                   |
|ADJUSTED (b)           |   2.6%         2.2%         4.3%         0.0%      |   2.6%         8.0%         5.1%        11.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    1/9 (11%)    0/9 (0%)   |  0/9 (0%)     0/8 (0%)     0/9 (0%)     0/6 (0%)   |
|FIRST INCIDENCE (DAYS) |   727 (T)      727 (T)      456 (I)      ---       |   734 (T)      612          734 (T)      728       |
|LIFE TABLE             |  P=0.372N     P=0.724N     P=0.482      P=0.485N   |  P=0.120      P=0.276      P=0.509      P=0.137    |
|INCIDENTAL TUMOR       |  P=0.372N     P=0.724N     P=0.482      P=0.485N   |  P=0.080      P=0.249      P=0.509      P=0.140    |
|LOGISTIC REGRESSION    |  P=0.365N     P=0.724N     P=0.499      P=0.485N   |  P=0.108      P=0.293      P=0.509      P=0.142    |
|FISHER EXACT           |               P=0.752N     P=0.494      P=0.500N   |               P=0.303      P=0.494      P=0.103    |
|FIRST INCIDENCE (DAYS) |   727 (T)      727 (T)      456 (I)      727 (T)   |   734 (T)      612          734 (T)      728       |
|LIFE TABLE             |  P=0.586      P=0.724N     P=0.482      P=0.745N   |  P=0.120      P=0.276      P=0.509      P=0.137    |
|INCIDENTAL TUMOR       |  P=0.586      P=0.724N     P=0.482      P=0.745N   |  P=0.080      P=0.249      P=0.509      P=0.140    |
|LOGISTIC REGRESSION    |  P=0.589      P=0.724N     P=0.499      P=0.745N   |  P=0.108      P=0.293      P=0.509      P=0.142    |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|TUMOR RATES            |                                                    |    #            #            #            #        |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/9 (0%)     0/8 (0%)     0/9 (0%)     0/6 (0%)   |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          ---          734 (T)      734 (T)   |
|LIFE TABLE             |                                                    |  P=0.291        (e)        P=0.130      P=0.525    |
|INCIDENTAL TUMOR       |                                                    |  P=0.291        (e)        P=0.130      P=0.525    |
|LOGISTIC REGRESSION    |                                                    |  P=0.291        (e)        P=0.130      P=0.525    |
|FISHER EXACT           |                                                    |                 (e)        P=0.122      P=0.500    |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|FIRST INCIDENCE (DAYS) |   727 (T)      ---          727 (T)      ---       |   ---          734 (T)      ---          ---       |
|LIFE TABLE             |  P=0.186N     P=0.203N     P=0.509N     P=0.222N   |  P=0.542N     P=0.484        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.186N     P=0.203N     P=0.509N     P=0.222N   |  P=0.542N     P=0.484        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.186N     P=0.203N     P=0.509N     P=0.222N   |  P=0.542N     P=0.484        (e)          (e)      |
|FISHER EXACT           |               P=0.248N     P=0.500N     P=0.248N   |               P=0.500        (e)          (e)      |
|OVERALL (a)            |  7/60 (12%)   3/60 (5%)    2/60 (3%)    2/60 (3%)  |  2/60 (3%)    0/60 (0%)    1/60 (2%)    1/60 (2%)  |
|ADJUSTED (b)           |  15.8%         6.5%         5.3%         4.3%      |   4.6%         0.0%         2.4%         2.3%      |
|TERMINAL (d)           |  4/39 (10%)   3/46 (7%)    2/38 (5%)    1/42 (2%)  |  1/38 (3%)    0/35 (0%)    0/40 (0%)    1/43 (2%)  |
|FIRST INCIDENCE (DAYS) |   595          727 (T)      727 (T)      589       |   461          ---          723          734 (T)   |
|INCIDENTAL TUMOR       |  P=0.027N*    P=0.153N     P=0.064N     P=0.027N*  |  P=0.439N     P=0.112N     P=0.448N     P=0.353N   |
|LOGISTIC REGRESSION    |  P=0.048N*    P=0.151N     P=0.085N     P=0.067N   |  P=0.500N     P=0.232N     P=0.503N     P=0.502N   |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|FIRST INCIDENCE (DAYS) |   595          727 (T)      727 (T)      589       |   461          734 (T)      723          734 (T)   |
|LIFE TABLE             |  P=0.023N*    P=0.041N*    P=0.073N     P=0.027N*  |  P=0.370N     P=0.519N     P=0.488N     P=0.471N   |
|INCIDENTAL TUMOR       |  P=0.010N*    P=0.053N     P=0.051N     P=0.008N** |  P=0.348N     P=0.374N     P=0.448N     P=0.353N   |
|LOGISTIC REGRESSION    |  P=0.020N*    P=0.057N     P=0.067N     P=0.023N*  |  P=0.405N     P=0.498N     P=0.503N     P=0.502N   |
|COCHRAN-ARMITAGE       |  P=0.023N*                                         |  P=0.409N                                          |
|FISHER EXACT           |               P=0.063N     P=0.063N     P=0.027N*  |               P=0.500N     P=0.500N     P=0.500N   |
|     Histiocytic Sarcoma                                                                                                         |
|FIRST INCIDENCE (DAYS) |   ---          727 (T)      657          727 (T)   |   673          562          618          418       |
|LIFE TABLE             |  P=0.366      P=0.533      P=0.240      P=0.515    |  P=0.277      P=0.673      P=0.526      P=0.393    |
|INCIDENTAL TUMOR       |  P=0.244      P=0.533      P=0.232      P=0.515    |  P=0.155      P=0.690N     P=0.510      P=0.484    |
|LOGISTIC REGRESSION    |  P=0.361      P=0.533      P=0.236      P=0.515    |  P=0.219      P=0.693      P=0.509      P=0.338    |
|FISHER EXACT           |               P=0.500      P=0.248      P=0.500    |               P=0.691N     P=0.500      P=0.340    |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated                                               |
|     Cell Type                                                                                                                   |
|OVERALL (a)            |  4/60 (7%)    2/60 (3%)    6/60 (10%)   4/60 (7%)  |  3/60 (5%)    9/60 (15%)  10/60 (17%)   8/60 (13%) |
|ADJUSTED (b)           |  10.3%         4.3%        14.9%         8.7%      |   7.1%        22.7%        24.3%        18.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/9 (0%)     1/9 (11%)  |  0/9 (0%)     0/8 (0%)     0/9 (0%)     0/6 (0%)   |
|TERMINAL (d)           |  4/39 (10%)   2/46 (4%)    4/38 (11%)   3/42 (7%)  |  1/38 (3%)    5/35 (14%)   9/40 (23%)   7/43 (16%) |
|FIRST INCIDENCE (DAYS) |   727 (T)      727 (T)      673          456 (I)   |   582          668          718          728       |
|LIFE TABLE             |  P=0.433      P=0.264N     P=0.356      P=0.614N   |  P=0.271      P=0.061      P=0.050 *    P=0.150    |
|INCIDENTAL TUMOR       |  P=0.370      P=0.264N     P=0.357      P=0.614N   |  P=0.200      P=0.092      P=0.044 *    P=0.095    |
|LOGISTIC REGRESSION    |  P=0.420      P=0.264N     P=0.352      P=0.641    |  P=0.229      P=0.060      P=0.044 *    P=0.125    |
|FISHER EXACT           |               P=0.340N     P=0.372      P=0.641N   |               P=0.063      P=0.037 *    P=0.102    |
|     Benign Tumors                                                                                                               |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   2/10 (20%)   3/9 (33%)    1/9 (11%)  |  1/9 (11%)    0/8 (0%)     2/9 (22%)    0/6 (0%)   |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      409          456 (I)   |   457 (I)      598          457 (I)      728       |
|LIFE TABLE             |  P=0.058N     P=0.553N     P=0.500      P=0.101N   |  P=0.069N     P=0.247      P=0.365      P=0.152N   |
|INCIDENTAL TUMOR       |  P=0.045N*    P=0.248      P=0.571N     P=0.143N   |  P=0.147N     P=0.270      P=0.283      P=0.270N   |
|LOGISTIC REGRESSION    |  P=0.052N     P=0.273      P=0.544      P=0.121N   |  P=0.100N     P=0.320      P=0.321      P=0.182N   |
|FISHER EXACT           |               P=0.227      P=0.573N     P=0.137N   |               P=0.355      P=0.289      P=0.283N   |
|     Malignant Tumors                                                                                                            |
|FIRST INCIDENCE (DAYS) |   595          619          409          456 (I)   |   461          457 (I)      548          418       |
|LIFE TABLE             |  P=0.519N     P=0.488N     P=0.278      P=0.509N   |  P=0.514N     P=0.198      P=0.366      P=0.458    |
|INCIDENTAL TUMOR       |  P=0.461N     P=0.463      P=0.348      P=0.412N   |  P=0.225      P=0.327      P=0.290      P=0.292    |
|LOGISTIC REGRESSION    |  P=0.484N     P=0.326      P=0.275      P=0.566    |  P=0.165      P=0.186      P=0.189      P=0.332    |
|FISHER EXACT           |               P=0.425      P=0.287      P=0.576N   |               P=0.221      P=0.281      P=0.281    |
|     Malignant and Benign Tumors                                                                                                 |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   2/10 (20%)   3/9 (33%)    3/9 (33%)  |  1/9 (11%)    1/8 (13%)    2/9 (22%)    0/6 (0%)   |
|FIRST INCIDENCE (DAYS) |   456 (I)      456 (I)      409          456 (I)   |   457 (I)      457 (I)      457 (I)       82       |
|INCIDENTAL TUMOR       |  P=0.358N     P=0.121      P=0.213      P=0.493N   |  P=0.365N     P=0.063      P=0.208      P=0.542N   |
|LOGISTIC REGRESSION    |  P=0.331N     P=0.091      P=0.159      P=0.520N   |  P=0.247N     P=0.033 *    P=0.154      P=0.515N   |
|FISHER EXACT           |               P=0.156      P=0.211      P=0.500N   |               P=0.066      P=0.229      P=0.573N   |
(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).